The effect of lifestyle-based education to women and their husbands on the anxiety and depression during pregnancy: a randomized controlled trial

Objective: The aim of this study was to determine the effect of lifestyle-based education to women and their husbands on anxiety and depression during pregnancy.

Method: This controlled trial was conducted on 189 pregnant women. Participants were allocated into three groups through block randomization. In the first intervention group, both women and their husbands, and in the second one, only women received the lifestyle-based education. In the control group, women received only the routine care. Edinburgh depression and Spielberger anxiety questionnaires were completed at baseline and 8 weeks after it.

Results: Compared to the control group, significant reductions were observed in the scores of depression (adjusted difference: ?4.7; 95% CI: ?5.9 to ?3.4), state anxiety (?8.1; ?11.3 to ?4.9) and trait anxiety (?8.3; ?11.9 to ?5.0) in the first intervention group, and in the scores of depression (?2.9; ?4.1 to ?1.6), state anxiety (?4.3; ?7.5 to ?1.1) and trait anxiety (?5.5; 95% CI: ?8.7 to ?2.3) in the second intervention group. Comparing the two intervention groups, mean scores of depression and state anxiety were significantly lower in the first group.

Conclusion: Results suggested the positive effect of lifestyle education to women and their husbands on depression and anxiety during pregnancy.     

The effect of inhaled corticosteroids on hypothalamic-pituitary-adrenal axis

Objectives:

The aim of this study was to compare systemic effects of high-dose fluticasone propionate (FP) and beclomethasone dipropionate (BDP) via pressurized metered dose inhaler on adrenal and pulmonary function tests.

Materials and Methods:

A total of 66 patients with newly diagnosed moderate persistent asthma without previous use of asthma medications participated in this single blind, randomized, parallel design study. FP or BDP increased to 1 500 μg/d in 62 patients who had not received oral or IV corticosteroids in the previous six months. Possible effects of BDP and FP on adrenal function were evaluated by free cortisol level at baseline and after Synacthen test (250 μg). Fasting plasma glucose and pulmonary function tests were also assessed. Similar tests were repeated 3 weeks after increasing dose of inhaled corticosteroids to 1 500 μg/d.

Results:

No statistically significant suppression was found in geometric means of cortisol level post treatment in both groups. After treatment in FP group, mean forced expiratory volume in one second (FEV1) and mean forced vital capacity (FVC) values improved by 0.17 l (5.66% ± 13.91, P=0.031) and 0.18 l (5.09% ± 10.29, P=0.010), respectively. Although FEV1 and FVC improved in BDP group but was not statistically significant. Oral candidiasis and hoarseness were observed in 6.5% patients receiving BDP, but hoarseness was found in 3.2% patients in FP group (P=0.288).

Conclusions:

The results indicate that safety profiles of high doses of BDP and FP with respect to adrenal function are similar, but FP is more efficacious than that of BDP in improving pulmonary function test.KEY WORDS: Adrenal cortex function tests, adrenal insufficiency, asthma, beclomethasone dipropionate, fluticasone     

Biodegradable multiblock poly(N-2-hydroxypropyl)methacrylamide gemcitabine and paclitaxel conjugates for ovarian cancer cell combination treatment

The synthesis, characterization, and in vitro evaluation of a combination delivery of multiblock poly(N-2-hydroxypropyl)methacrylamide (HPMA), gemcitabine (GEM) and paclitaxel (PTX) conjugates is described in this study. Multiblock copolymer conjugates of a large molecular weight (M_w > 200 kDa) were studied and compared to traditional, small molecular weight (M_w < 45 kDa) conjugates. Stability of the conjugates in different pH was assessed, and their cytotoxicity in combination toward A2780 human ovarian cancer cells was evaluated by combination index analysis. Treatment duration (4 and 72 h) and sequence of addition were explored. In addition, an HPMA copolymer conjugate with both GEM and PTX in the side chains was evaluated in a similar manner and compared to a physical mixture of individual conjugates. Conjugates with narrow molecular weight distribution (M_w/M_n < 1.1) were obtained via RAFT polymerization, and drug loadings of between 5.5 and 9.2 wt% were achieved. Conjugates demonstrated moderate stability with less than 65% release over 24 h at pH 7.4, and near complete drug release in the presence of the lysosomal enzyme cathepsin B in 3 h. In combination, the cytotoxic effects of a mixture of the conjugates were primarily additive. Synergistic effects were observed when A2780 human ovarian cancer cells were treated simultaneously for 4 h with multiblock conjugates (CI < 0.7). When both GEM and PTX were conjugated to the same copolymer backbone, moderate antagonism (CI 1.3–1.6) was observed. These results demonstrate that multiblock HPMA copolymer–GEM and –PTX conjugates, when delivered as a mixture of individual agents, are promising for the treatment of ovarian cancer.     

Technetium-99m-Labeled N-(2-Hydroxypropyl) Methacrylamide Copolymers: Synthesis,Characterization, and in Vivo Biodistribution

PURPOSE: To synthesize novel technetium-99m (99mTc)-labeled N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers and characterize the effect of charge and molecular weight on their biodistribution in SCID mice. METHODS: Electronegative and neutral 7-kDa, 21-kDa, and 70-kDa HPMA copolymers containing a 99mTc chelating comonomer, bearing N-omega-bis(2-pyridylmethyl)-L-lysine (DPK), were synthesized by free-radical precipitation copolymerization. The copolymers were labeled via 99mTc tricarbonyl chelation to DPK-bearing comonomer. They were characterized by side-chain content, molecular weight, molecular weight distribution, radiochemical purity, and labeling stability. Scintigraphic images were obtained during the first 90 min and at 24 h postintravenous injection in SCID mice. At 24 h, organ radioactivity was determined from necropsy tissue counting. RESULTS: 99mTc-labeled HPMA copolymers showed greater than 90% stability over a 24-h challenge with cysteine and histidine. Scintigraphic images and the necropsy data showed that the negatively charged copolymers were eliminated from the body significantly faster than the neutral copolymers in a size-dependent manner. CONCLUSIONS: To facilitate clinical scintigraphic imaging, stable chelation of 99mTc may be achieved by incorporation of a DPK-bearing comonomer into the HPMA backbone. Electronegative and neutral 99mTc-labeled HPMA copolymers of 7, 21, and 70 kDa show significant variation in organ biodistribution in SCID mice. 99mTc-labeled HPMA copolymers could be used as diagnostic agents and to study pharmacokinetics of delivery systems based on these copolymers.     

The prevalence of obesity and its related risk factor in the north of iran in 2006

Background: The main objective of this study was to evaluate the prevalence of the obesity and the related risk factors in the north of Iran. Methods: This was a population-based cross-sectional study that enrolled 2495 subjects (1247 males and 1248 females) using stratified cluster sampling. Interviewers recorded the data using a multidimensional questionnaire including anthropometric indexes. Body mass index equal to or greater than 25 was considered as overweight and that of 30 and 40 as obese and pathologic obese respectively. SPSS 16.0 software was used for statistical data analysis. Results: Mean age of the subjects was 39.2 [95% CI: 38.6, 39.8] yr. Mean body mass index was 25.3 [95% CI: 25.0, 25.6] kg/m(2) for men and 27.5 [95% CI: 27.2, 27.9] kg/m2 for women. The prevalence rates of overweight, obesity and pathologic obesity were 29.9% (745/2495), 22.5% (561/2495) and 1.8% (44/2495) respectively. The prevalence of obesity was higher in urban residents than rural ones, 27.3% versus 18.9% respectively (P<0.001). The prevalence rates of obesity and pathologic obesity were much higher in women than men were, 30.3% versus 15.4% and 3.0% versus 0.6% respectively (P=0.001). The odds ratio estimate was 1.68 [95% CI: 1.40, 2.02] for urban area compared to rural area; 2.60 [95% CI: 2.14, 3.15] for females compared to males; 5.95 [95% CI: 3.54, 9.99] for married people compared to single people; 1.89 [95% CI: 1.44, 2.84] for age group of 55-65 years compared to age group of 15-24 years; 1.76 [95% CI: 1.17, 2.64] for illiterate people compared to those who had academic education; 1.98 [95% CI: 1.13, 2.49] for poor people compared to people with high economic level. Conclusion: The prevalence of obesity and overweight is very high in the north of Iran, hence is a signal of serious health problem, and should be the focus of special attention.     

Lifestyle-Related Determinants of Hookah and Cigarette Smoking in Iranian Adults

To identify lifestyle-related determinants of hookah and cigarette smoking in Iranian adults, a total of 12,514 men and women aged ≥19 years in three counties in central Iran (Isfahan, Najafabad, Arak) were selected in multistage random sampling. Data on socio-demographic characteristics and lifestyle were collected in interviewer-administered questionnaires, as part of the baseline survey of the Isfahan Healthy Heart Program. Unhealthy lifestyle-related factors independently associated with cigarette and hookah smoking, were identified in sex-specific multivariate logistic regression analyses. High stress levels (OR: 1.55; 95% CI: 1.35–1.78 for men; OR: 1.63; 95% CI: 1.17–2.27 for women), family member smoking (OR: 1.61; 95% CI: 1.27–4.92 for men; OR: 2.49; 95% CI: 2.20–2.95 for women), and short/long sleep duration (OR: 1.18; 95% CI: 1.01–1.39 for men; OR: 1.52; 95% CI: 1.10–2.35 for women) were associated with cigarette smoking in both men and women. Poor diet was also related to cigarette smoking in men (OR: 1.55; 95% CI: 1.62–1.89). Family member smoking was associated with hookah smoking in both men (OR: 1.16; 95% CI: 1.05–3.12) and women (OR: 1.56; 95% CI: 1.02–4.92), and in addition high stress levels (OR: 2.87; 95% CI: 1.14–5.83) and short/long sleep duration (OR: 1.07; 95% CI: 1.02–2.41) were associated with hookah smoking in women. Unhealthy lifestyle-related factors co-occur with cigarette and hookah smoking in Iranian adults, likely increasing the risk for chronic health problems. Sex differences in the determinants of hookah and cigarette smoking may need to be taken into account in planning tobacco control strategies.     

Nanocarriers for nuclear imaging and radiotherapy of cancer

Several nanoscale carriers (nanoparticles, liposomes, water-soluble polymers, micelles and dendrimers) have been developed for targeted delivery of cancer diagnostic and therapeutic agents. These carriers can selectively target cancer sites and carry large payloads, thereby improving cancer detection and therapy effectiveness. Further, the combination of newer nuclear imaging techniques providing high sensitivity and spatial resolution such as dual modality imaging with positron emission tomography/computed tomography (PET/CT) and use of nanoscale devices to carry diagnostic and therapeutic radionuclides with high target specificity can enable more accurate detection, staging and therapy planning of cancer. The successful clinical applications of radiolabeled monoclonal antibodies for cancer detection and therapy bode well for the future of nanoscale carrier systems in clinical oncology. Several radiolabeled multifunctional nanocarriers have been effective in detecting and treating cancer in animal models. Nonetheless, further preclinical, clinical and long-term toxicity studies will be required to translate this technology to the care of patients with cancer. The objective of this review is to present a brief but comprehensive overview of the various nuclear imaging techniques and the use of nanocarriers to deliver radionuclides for the diagnosis and therapy of cancer.     

Water-soluble polymers for targeted drug delivery to human squamous carcinoma of head and neck

Human squamous cell carcinoma of the head and neck (SCCHN) is characterized by over expression of a tumor cell surface-specific receptor namely Hsp47/CBP2 that makes it a favorable candidate for targeted delivery of anticancer drugs. Several synthetic peptides have been identified as effective ligands for binding to CBP2. The purpose of this study is to investigate the potential of water-soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-doxorubicin (Dox) conjugates containing a Hsp47/CBP2 binding peptide sequence, namely WHYPWFQNWAMA for targeted delivery to SCCHN. An HPMA copolymer containing Dox and CBP2 targeting peptide conjugated via lysosomally degradable glycylphenylalanylleucylglycine (GFLG) spacer was synthesized by free radical precipitation copolymerization. A control polymer without targeting moiety was also synthesized. The conjugates were characterized for drug content, peptide content, molecular weight and molecular weight distribution. The uptake of polymeric conjugates by both drug resistant and drug sensitive SCCHN cells were determined in vitro by flow cytometry using FACS scan analysis. Cytotoxicity of the conjugates towards drug sensitive as well as multidrug resistant SCCHN cells were evaluated by a clonal survival assay and compared to free Dox. The cytotoxicity of the free peptide was similarly evaluated. The internalization and subcellular fate of the conjugates in drug sensitive SCCHN cells was monitored using confocal microscopy. The new targetable copolymer contained 0.16 mmole peptide/g polymer. Studies on drug sensitive SCCHN cells demonstrated lesser uptake of both targeted and non-targeted conjugates compared to free Dox suggesting a slower endocytic mechanism of uptake for the conjugates as opposed to rapid diffusion of free Dox. At higher Dox equivalent concentrations (>20 microM) the targeted conjugate showed significantly higher uptake (p < or = 0.028) than the non-targeted conjugate. The uptake of the targeted conjugate was inhibited in the presence of an anti Hsp47 antibody suggesting the involvement of active receptor mediated endocytosis in cell entry of the conjugate. Compared to free Dox, the targeted and non-targeted conjugates caused marginally lower inhibition (p < or = 0.01) of the drug sensitive SCCHN cells. In contrast, the same conjugates showed significantly higher uptake (p < or = 0.004) by drug resistant SCCHN cells and caused significantly higher inhibition (p < or = 0.02) of drug resistant SCCHN cells when compared to free Dox. Results suggest that the polymeric conjugates were able to overcome drug resistance. Confocal microscopy studies demonstrated the uptake of the polymeric conjugates, followed by internalization, intralysosomal localization and subsequent release of Dox. HPMA copolymer-Dox-peptide conjugates targeted to SCCHN cells were able to overcome drug resistance and increase efficacy in vitro. The results suggest that targetable polymeric conjugates have potential to improve systemic head and neck cancer chemotherapy by increasing tumor localization and reducing dose-limiting toxicity.     

The effects of smoking on corneal endothelial cells: a cross-sectional study on a population from Isfahan,Iran

Purpose: The aim of this study is to compare the effect of smoking in corneal endothelial cell number and morphology by specular microscopy on a non-smoker population.

Methods: Our cross-sectional study was performed on 150 participants from a non-smoker population. Non-contact specular microscopy (Tomey Corporation Inc., Nagoya, Japan) was performed in the center of the cornea of all subjects. The cell density (CD), average cell size (AVG), percent of hexagonality (HEX%) and central corneal thickness (CCT) were calculated and compared in both groups.

Results: Totally, 76 eyes of 76 smokers and 74 eyes of 74 non-smokers were enrolled in the study from 2015 to 2016. The mean age of smokers and non-smokers were 48.61?±?17.04 and 46.39?±?13.02, respectively. The mean number of pack/year among the smokers was 17.36?±?14.68. Also, the mean values of AVG and CD were significantly different for these two groups (p?=?0.011 and p?=?0.039, respectively). Other corneal endothelial variables did not show a significant difference between smokers and non-smokers (p?>?0.05). However, smokers with severe nicotine dependency had significantly greater AVG and lower CD in comparison with the non-smokers (p?=?0.004 and p?=?0.013, respectively).

Conclusion: Our study showed that smoking can cause significant changes in some of the corneal endothelial variables, but not all of them.     

PEG-Benzaldehyde-Hydrazone-Lipid Based PEG-Sheddable pH-Sensitive Liposomes: Abilities for Endosomal Escape and Long Circulation

Purpose

To fabricate an acid-cleavable PEG polymer for the development of PEG-cleavable pH-sensitive liposomes (CL-pPSL), and to investigate their ability for endosomal escape and long circulation.

Methods

PEG-benzaldehyde-hydrazone-cholesteryl hemisuccinate (PEG_B-Hz-CHEMS) containing hydrazone and ester bonds was synthesised and used to fabricate a dual pH-sensitive CL-pPSL. Non-cleavable PEGylated pH-sensitive liposome (pPSL) was used as a reference and gemcitabine as a model drug. The cell uptake and endosomal escape were investigated in pancreatic cancer Mia PaCa-2 cells and pharmacokinetics were studied in rats.

Results

The CL-pPSL showed accelerated drug release at endosomal pH 5.0 compared to pPSL. Compared to pPSL, CL-pPSL released their fluorescent payload to cytosol more efficiently and showed a 1.4-fold increase in intracellular gemcitabine concentration and higher cytotoxicity. In rats, injection of gemcitabine loaded CL-pPSL resulted in a slightly smaller V_d (149?±?27 ml/kg; 170?±?30 ml/kg) and shorter terminal T_1/2 (5.4?±?0.3 h; 5.8?±?0.6 h) (both p?>?0.05) but a significantly lower AUC (p?<?0.01), than pPSL, due to the lower PEGylation degree (1.7 mol%) which means a ‘mushroom’ configuration of PEG. A five-time increase in the dose with CL-pPSL resulted in a 11-fold increase in AUC and a longer T_1/2 (8.2?±?0.5 h).

Conclusion

The PEG-detachment from the CL-pPSL enhanced endosome escape efficiency compared with pPSL, without significantly compromising their stealth abilities.