Multi-variate multi-objective optimization of production conditions for electro-spun skin scaffold using RSM and investigation of gamma irradiation effects on the properties of the optimized sample.

Developing electro-spun scaffolds with ideal mechanical properties for skin purposes can profit from using the Response Surface Methodology technique to define and optimize the outcome quality and required sterilization for use in vivo. This study investigated the effects of four main independent electrospinning variables for polycaprolactone nanofibers scaffold using multi-variable and multi-objective optimization. It was done to determine significant parameters on responses and find optimal conditions to reach the preferred properties. Young's modulus, elongation-at-break, and tensile strength were the responses. After obtaining appropriate models, the impact share of variables on the responses was determined using Sobol sensitivity analysis. The results showed that flow rate is the most significant parameter of elastic modulus and tensile strength responses, with 76.45 % and 41.27 % impact shares, respectively. The polymer concentration is the following significant parameter on elongation at break, tensile strength and, Young's modulus responses with 64.35 %, 39.485 and, 14.28 % impact share, respectively. Based on the optimized results, a skin scaffold with desired mechanical properties was achieved (under solution concentration of 10 % w/v, flow rate of 2 mL/h, nuzzle-collector distance of 15 cm, and applied voltage of 20 kV). Then it was sterilized with gamma radiation of various doses (25, 40, and 55 kGy) to use in vivo. The SEM analysis indicated no significant change in fibrous morphology due to gamma irradiation at any dosage. FTIR analysis demonstrated the breakup of ester bonds due to gamma irradiation. For samples irradiated by 25 kGy, the crystallinity percentage decreased and chains crosslinking without losing the mechanical stability was dominant. The studies demonstrated that 25 kGy of gamma irradiation could improve the mechanical properties of the optimized PCL skin scaffold, which is very promising for wound healing.

Double-pulsed wave packets in spontaneous radiation from a tandem undulator.

We verify that each wave packet of spontaneous radiation from two undulators placed in series has a double-pulsed temporal profile with pulse spacing which can be controlled at the attosecond level. Using a Mach-Zehnder interferometer operating at ultraviolet wavelengths, we obtain the autocorrelation trace for the spontaneous radiation from the tandem undulator. The results clearly show that the wave packet has a double-pulsed structure, consisting of a pair of 10-cycle oscillations with a variable separation. We also report the characterization of the time delay between the double-pulsed components in different wavelength regimes. The excellent agreement between the independent measurements confirms that a tandem undulator can be used to produce double-pulsed wave packets at arbitrary wavelength.

Association of NAD (P) H Quinine Oxidoreductase 1 rs1800566 Polymorphism with Bladder and Prostate Cancers - a Systematic Review and Meta-Analysis.

BACKGROUND: Number of studies has been performed to investigate the association of NAD (P) H quinine oxidoreductase 1 (NQO1) rs1800566 polymorphism with risk of bladder and prostate cancers, but presented inconsistent results. Therefore, we performed a meta-analysis to provide a comprehensive data on the association of NQO1 rs1800566 polymorphism with bladder and prostate cancers. METHODS: All eligible studies were identified in PubMed, Google Scholar, EMBASE, and China National Knowledge Infrastructure databases before June 01, 2019. RESULTS: A total of 22 case-control studies including 15 studies with 4,413 cases and 4,275 controls on bladder cancer and 7 studies with 762 cases and 1,813 controls on prostate cancer were selected. Overall, pooled data showed that the NQO1 rs1800566 polymorphism was significantly associated with an increased risk of bladder cancer (T vs. C: OR 1.300; 95% CI 1.112-1.518; P = 0.001; TT vs. CC: OR 1.415; 95% CI 1.084-1.847; P = 0.011; TC vs. CC: OR 1.389; 95% CI 1.111-1.738; P = 0.004; TT + TC vs. CC: OR 1.428; 95% CI 1.145-1.782; P = 0.002) and prostate cancer (TC vs. CC: OR 1.276; 95% CI 1.047-1.555; P = 0.016; TT + TC vs. CC: OR 1.268; 95% CI 1.050-1.532; P = 0.014). The stratified analysis by ethnicity revealed an increased risk of bladder cancer among Caucasians and prostate cancer among Asians. CONCLUSION: This meta-analysis suggested that the NQO1 rs1800566 polymorphism was significantly associated with increased risk of bladder and prostate cancers.

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization.

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented.

Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications

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Relationship between leptin concentration and body fat with peripheral blood mononuclear cells cytokines among obese and overweight adults.

BACKGROUND: Overweight and obesity has been suggested to be well correlated with altered levels of pro-inflammatory cytokines. AIM: The purpose of this study is to assess the relationship of body fat mass (BFM), body fat percentage (BFP) and leptin levels with peripheral blood mononuclear cells (PBMCs) cytokines among obese and overweight adults. METHODS: Eighty-two overweight and obese individuals were divided into two BMI-category groups (BMI <30 and BMI ≥30 kg/m2) in this study. Balanced blocked randomization was used based on their sex and BMI ranges. Fasting blood samples, PBMCs cytokines, leptin and anthropometric indices were measured and PBMCs were cultured. RESULTS: Mean of leptin concentrations were 23.14 ± 4.07 and 28.25 ± 4.35 pg/ml among individuals with BMI <30 and BMI ≥30 kg/m2, respectively. The mean values of anthropometric measurements (all P < 0.001), the concentrations of TNF-α (P = 0.028) and IFN-γ (P = 0.029) were significantly higher among obese individuals. BFP had a significant positive correlation with leptin (P < 0.001, r = 0.445) and TGF-ß (P = 0.03, r = 0.243). BFM has significant positive correlation with leptin (P < 0.001, r = 0.521). Leptin had a positive significant correlation with IFN-γ (p = 0.03, r = 0.251). CONCLUSIONS: Regarding these results, we proved that BFP, BFM and leptin levels have significant correlations with some PBMC cytokines. Focusing on such strategies may lead to promises for alleviating obesity and its co-morbidities.

Comparison of various classifications for patients with common variable immunodeficiency (CVID) using measurement of B-cell subsets.

BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications.

Genetic diversity and vector transmission of phytoplasmas associated with sesame phyllody in Iran.

During 2010-14 surveys in the major sesame growing areas of Fars, Yazd and Isfahan provinces (Iran), genetic diversity and vector transmission of phytoplasmas associated with sesame phyllody were studied. Virtual RFLP, phylogenetic, and DNA homology analyses of partial 16S ribosomal sequences of phytoplasma strains associated with symptomatic plants revealed the presence of phytoplasmas referable to three ribosomal subgroups, 16SrII-D, 16SrVI-A, and 16SrIX-C. The same analyses using 16S rDNA sequences from sesame phyllody-associated phytoplasmas retrieved from GenBank database showed the presence of phytoplasmas clustering with strains in the same subgroups in other Iranian provinces including Bushehr and Khorasan Razavi. Circulifer haematoceps and Orosius albicinctus, known vectors of the disease in Iran, were tested for transmission of the strains identified in this study. C. haematoceps transmitted 16SrII-D, 16SrVI-A, and 16SrIX-C phytoplasmas, while O. albicinctus only transmitted 16SrII-D strains. Based on the results of the present study and considering the reported presence of phytoplasmas belonging to the same ribosomal subgroups in other crops, sesame fields probably play an important role in the epidemiology of other diseases associated with these phytoplasmas in Iran.

Myocardial capillary density in normal and diabetic male rats: Effect of bezafibrate.

Cardiovascular disease is the common cause of mortality in diabetic subjects. Recently, it is indicated that peroxisome proliferator-activated receptors (PPARs) agonists have beneficial effect on cardiovascular system especially on angiogenesis. PPARs have three isotypes: PPARα, PPARß/δ and PPARγ. In this study, we evaluated the effect of bezafibrate as pan PPAR agonist on myocardial capillary density in type I diabetic rats. Eighteen male wistar rats were randomly divided into three groups (n=6 each): control, diabetic and diabetic+bezafibrate (400 mg/kg/day) by gavage every day. Diabetes was induced by a single dose of streptozotocin (55 mg/kg), intraperitoneally. After 21 days, capillary density in the myocardial tissue was evaluated by immunohistochemical staining and reported as capillaries per mm(2). Blood samples were taken before and after the experiment. Diabetes was associated by lower serum nitric oxide (NO) concentration and reduced myocardial capillary density compared to control group (121.71 ± 13.32 vs. 158.78 ± 11.08 /mm(2); P<0.05). Administration of bezafibrate significantly increased serum NO level and improved angiogenesis in myocardial tissue of diabetic animals (170.24 ± 15.76 vs.121.71 ± 13.32 /mm(2); P<0.05). There was a positive correlation between serum NO concentration and myocardial capillary density (r=0.90). Activation of all isotypes of PPAR by bezafibrate improves heart capillary density in diabetic animals and it seems that it can be considered for treatment or prevention of coronary heart disease in diabetic subjects.

Stochastic nature of series of waiting times.

Although fluctuations in the waiting time series have been studied for a long time, some important issues such as its long-range memory and its stochastic features in the presence of nonstationarity have so far remained unstudied. Here we find that the "waiting times" series for a given increment level have long-range correlations with Hurst exponents belonging to the interval 1/2

Pan-PPAR Agonist, Bezafibrate, Restores Angiogenesis in Hindlimb Ischemia in Normal and Diabetic Rats.

Introduction. The aim of this study was to investigate the effect of bezafibrate as a pan-PPAR agonist on angiogenesis and serum nitrite, the main metabolite of nitric oxide (NO), vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) concentrations in hindlimb ischemia model of normal and type I diabetic rats. Methods. 28 male Wistar rats were divided into control and diabetic groups. Then, all rats underwent unilateral hindlimb ischemia. After recovery, they were randomly assigned to one of the following experimental groups: (1) control; (2) control + bezafibrate (400 mg/kg/day); (3) diabetic; (4) diabetic + beztafibrate. After three weeks, blood samples were taken and capillary density was evaluated in the gasterocnemius muscle of ischemic limb. Results. Bezafibrate increased capillary density and capillary/fiber ratio in ischemic leg of diabetic and control rats (P < 0.05). Serum VEGF and VEGFR-2 concentrations did not alter after bezafibrate administration, however, serum nitrite concentration was significantly higher in bezafibrate-treated groups than non-treated groups (P < 0.05). Discussion. It seems that bezafibrate, as a pan PPAR agonist, restores angiogenesis in hindlimb ischemic diabetic animals and is useful for prevention and/or treatment of peripheral artery disease in diabetic subjects.

Role of peroxisome proliferator-activated receptor ß agonist on angiogenesis in hindlimb ischemic diabetic rats.

INTRODUCTION: Studies indicated that PPARß agonists play a role in modulation of angiogenesis. In this study, we evaluated the effect of specific PPARß agonist, GW0742, on angiogenesis and serum vascular endothelial growth factor (VEGF), VEGF receptor-2 (VEGFR-2), and nitrite concentrations in hindlimb ischemia in normal and diabetic rats. METHODS: Hindlimb ischemic rats were divided into four groups: control, diabetic, control, and diabetic treated with GW0742 (n=7 each). Diabetes was induced by injection of streptozotocin (55mg/kg, ip). GW0742 was injected 1day after surgery (1mg/kg, sc). After 21days, blood samples were taken, and gastrocnemius muscles were harvested for immunohistochemistry. RESULTS: GW0742 significantly increased serum nitrite and VEGFR-2 concentrations and VEGF-to-VEGFR-2 ratio in control and diabetic rats. Capillary density was lower in diabetic animals compared to the control, and GW0742 significantly restored the capillary density in the control and diabetic hindlimb ischemic rats. CONCLUSION: PPARß agonists restore skeletal muscle angiogenesis and can be considered for prevention and/or treatment of peripheral vascular complications in diabetic subjects.

The role of health environment and location in the emergence of urban criminal behaviours in tehran.

BACKGROUND: Although, the roots of criminal behaviours clearly lie in social, economic, and cultural factors, the increase criminal offences in urban settings has raised the issue of prevention through urban environmental health, planning and design. METHODS: The approach of the study was based on the scientific research methodology and indicators were compiled from observations and comparative analyses of those urban spaces that are most often the sites of crime. RESULTS: Pearson's correlation coefficient showed that 37% of sampled males and 51% of females emphasized on effectiveness of environmental factors. The urban space observations show that the environmental and physical factors affect on security and sensation of community safety among the citizens. CONCLUSION: Crime is committed in a particular place; place-related factors play a role in creating the potential for crimes to be committed. The results show the close bond between crimes and environmental problems.Recognition of the influence of location-specific characteristics and the correct environmental response may make it possible to prevent or at least reduce criminal acts in urban places.

Nationwide outbreak of listeriosis due to contaminated meat.

We used molecular subtyping to investigate an outbreak of listeriosis involving residents of 24 US states. We defined a case as infection with Listeria monocytogenes serotype 4b yielding one of several closely related patterns when subtyped by pulsed-field gel electrophoresis. Patients infected with strains yielding different patterns were used as controls. A total of 108 cases were identified with 14 associated deaths and four miscarriages or stillbirths. A case-control study implicated meat frankfurters as the likely source of infection (OR 17.3, 95% CI 2.4-160). The outbreak ended abruptly following a manufacturer-issued recall, and the outbreak strain was later detected in low levels in the recalled product. A second strain was recovered at higher levels but was not associated with human illness. Our findings suggest that L. monocytogenes strains vary widely in virulence and confirm that large outbreaks can occur even when only low levels of contamination are detected in sampled food. Standardized molecular subtyping and coordinated, multi-jurisdiction investigations can greatly facilitate detection and control of listeriosis outbreaks.

An outbreak of hepatitis A associated with green onions.

Forty-three cases of serologically confirmed hepatitis A occurred among individuals who ate at restaurant A in Ohio in 1998. Serum samples from all restaurant A employees who worked during the exposure period were negative for IgM antibodies to hepatitis A virus (HAV). A matched case-control study determined that foods containing green onions, which were eaten by 38 (95%) of 40 case patients compared with 30 (50%) of 60 control subjects, were associated with illness (matched odds ratio, 12.7; 95% confidence interval, 2.6-60.8). Genetic sequences of viral isolates from 14 case patients were identical to each other and to those of viral isolates from 3 patients with cases of hepatitis A acquired in Mexico. Although the implicated green onions, which could have come from one of 2 Mexican farms or from a Californian farm, were widely distributed, no additional green onion-associated cases were detected. More sensitive methods are needed to detect foodborne hepatitis A. A better understanding of how HAV might contaminate raw produce would aid in developing prevention strategies.

[Anesthesia for TUR procedures in the elderly]. / Die Anästhesie bei TUR-Eingriffen im Senium

Due to the increased life expectancy since the turn of the century also the urological interventions in patients of older age increased in number and thus in significance. Also when a smaller proportion of the TUR-interventions (in most cases only diagnostic measures) can be carried out in local anaesthesia, for the majority of cases a general anaesthesia or a central conduction anaesthesia is necessary. The particular characteristics of the anaesthesia in endovesical interventions, the pathophysiological peculiarities of the senium, the senile involution of the kidney, and a water and electrolyte balance often disturbed by urological complaints are among others the most important criteria which determine the choice of the anaesthesia in a senile patient when TUR-interventions are to be carried out. Based on an experience of many years, it is reported on the results of anaesthesia in 4,130 geriatric patients, among then 2,818 TUR-interventions. On account of the character of the TUR-interventions, of the age of the patient and the factors of risk even nowadays the central conduction anaesthesia, especially the spinal anaesthesia, is more often the method of choice.

[Special problems with anesthesia in urologic emergency surgery]. / Besonderheiten der Anästhesie bei urologischen Noteingriffen.

In the operative medicine the urological emergency interventions occupy a particular position. Apart from iatrogenic and/or emergency cases provoked by the external trauma, the life-threatening and urgent operations are very rare, in comparison to the other surgical disciplines. The maximum stress by anaesthesia of the urological emergency operations is, however, by far less and connected with considerable risks. In the analysis of 1,216 anaesthesias which were declared by the urologists as urgent operations it was shown that the frequency of anaesthesia accidents gradually increases from intact renal function up to uraemia and anuria. On account of less total stress in contraindications for the regional anaesthesia in urological emergency interventions the neuroleptanalgesia is to be preferred in comparison to the other anaesthesia methods.

[Anesthesia in pediatric urology]. / Die Anästhesie in der pädiatrischen Urologie.

It is reported on an experience of several years in 4,870 anaesthesias in the paediatric urology. Anaesthesiological peculiarities and anaesthetising techniques were critically represented, and the advantages of the induction of the anaesthesia with ketamines as well as the experiences made are described. Summarizing the following is established: 1. Among the urological patients and also in the anaesthetising techniques a fundamental change appeared. For the majority of the interventions in paediatric urology nowadays the anaesthesia is much simpler and less expensive than several years ago. 2. Inhalation anaesthesia is widely superseded by the dissociative anaesthesia with ketamine and the number of intubation anaesthesias considerably decreased. 3. During complicated and long lasting operations on newborn and infants the child is further on intubated and undergoes an assisted respiration. 4. When choosing the one or another anaesthetising method the character of the intervention in paediatric urology as such was authoritative and not the preference of the one or another anaesthetising method.