Characterization of integrons, extended spectrum beta lactamases and genetic diversity among uropathogenic Escherichia coli isolates from Kerman, south east of Iran.

Background and Objectives: The study aimed to investigate the distribution of genes encoding integrons, extended spectrum beta-lactamase (ESBL) in E. coli isolated from UTIs, as well as the genetic diversity among the isolates. Materials and Methods: E. coli isolates were recovered from the patients with UTI in Kerman Iran. Antibiotic susceptibility was done according to CLSI guidelines. The presence of ESBL genes and integrons was evaluated using PCR. PCR and sequencing were applied for the evaluation of cassette content of integrons. Genotyping of the isolates was performed by multiple-locus variable-number tandem repeat analysis (MLVA). Results: Imipenem was the most effective antibiotic, while the highest resistance was observed to streptomycin. In total 40.2% of isolates were ESBL producers. Of 69 integron-positive isolates, 59 only had class I integrons, 4 only had class II integrons and 6 had both types. The most common gene cassette found within class I integrons was dfrA17-aadA5 (n=27). The E. coli isolates were divided into 16 MLVA clusters. Conclusion: The current study demonstrated the simultaneous presence of class I integrons and ESBLs involved in the resistance of UPEC isolates to antibacterial agents. Our finding also revealed that the E. coli isolates belonged to diverse clones.

Berberine hydrochloride improves cognitive deficiency through hippocampal up-regulation of neurotrophins following inhalant self-administration of methamphetamine.

Objectives: Chronic methamphetamine (METH) abuse is recognized as an important risk factor for cognitive impairment. A plant-based isoquinoline alkaloid, Berberine hydrochloride (BER), shows memory and cognition enhancement properties. Due to the aim of the present study which is to investigate the influence of BER administration on METH-induced cognitive deficits, we investigated neurotrophin signaling including brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) as a possible mechanism by which BER exerts its cognitive improvement influences. Materials and Methods: In this experimental study, thirty-two male Wistar rats were randomly classified into four groups, including non-treated control, intubated control, METH-inhaled, and METH-inhaled + BER-intubated. Rats in the METH-inhaled group underwent METH inhalation for 14 days, and the BER-inhaled and BER-intubated rats were intubated (100mg/kg) for the following three weeks. A novel object recognition task (NORt) was carried out on days 36 and 37. Rats were sacrificed for histological preparations after the behavioral tests. Neurotrophic factors, including GDNF and BDNF, were evaluated by immunofluorescence staining in the hippocampus. Results: This experiment indicated a dramatic improvement in cognitive deficits associated with chronic METH abuse (P<0.001). Furthermore, a significant decrease in the expression of both neurotrophins, GDNF (P<0.001) and BDNF (P<0.001), was observed in the METH-inhaled group compared with the METH-inhaled group treated with BER and non-treated control group. Conclusion: Activation of neurotrophic factors after BER administration resulted in improvement of METH-induced cognitive deficits. Therefore, BER may be considered a promising treatment for METH users who experience cognition deficits.

Validation and Psychological Properties of the Persian Version of DSM 5 Yale Food Addiction Scale 2.0 (PYFAS 2.0) in Non-clinical Population.

Background: The Yale Food Addiction Scale version 2.0 (YFAS 2.0) is used for the assessment of food addiction (FA). This research intended to evaluate the validity of the Persian translation of the questionnaire and to investigate the psychological properties and the association between FA and anthropometric indices. Methods: In a sample of 473 nonclinical participants, FA, binge eating, and objectively measured anthropometric indices were assessed. Internal consistency, convergent, and validity of the PYFAS 2.0 were examined. Also, the factor structure (confirmatory factor analysis following the 11 diagnostic indicators in addition to the significant distress) and the construct of the scale were evaluated. Findings: The frequencies of mild, moderate, and severe FA based on PYFAS 2.0 were 0.2%, 10%, and 5.5%, respectively. The findings supported a one-factor structure. The confirmatory factor analysis revealed a good construct validity (RMSEA=0.043, χ2=76.38, df=41, χ2 (CMIN)/df=1.862, GFI=0.975, AGFI=0.957, IFI=0.986, RFI=0.958, ECVI=0.319, TLI=0.978). For both the diagnostic and symptom count versions, the PYFAS 2.0 presented acceptable internal consistency (IC) (Kuder-Richardson 20=0.99 and McDonald omega=0.91). Conclusion: The PYFAS 2.0 was a psychometrically sound instrument in an Iranian non-clinical population. This questionnaire can be used to study FA in Persian non-clinical populations. Future research should study the psychometric characteristics of this scale in high-risk groups.

Erythropoietin improve spatial memory impairment following methamphetamine neurotoxicity by inhibition of apoptosis, oxidative stress and neuroinflammation in CA1 area of hippocampus.

OBJECTIVE: Methamphetamine (METH) is one of the most widely used addictive drugs, and addiction to it is on the rise all over the world. METH abuse has long-term damaging effects that reduce memory and impair cognitive functions. According to studies, the observed effects are strongly related to the nerve cell damage caused by METH, which leads to neurotoxicity. Some of these intra-neuronal events include dopamine oxidation, excitotoxicity, and oxidative stress. Erythropoietin (EPO) is a hormone produced primarily by the kidneys and, in small quantities, by the liver. Studies have shown that EPO exhibits considerable neuroprotective effects. This study aimed to investigate the protective effects of EPO on METH neurotoxicity. METHODS: Initially, 48 male Wistar rats, weighing 250-300 g, were randomly assigned to four groups: control (n = 12), METH (n = 12), and METH+EPO (2500, 5000 IU/kg/IP- n = 12). METH was injected intraperitoneally at a dose of 40 mg per kg of body weight (four injections of 10 mg every two hours) to induce neurotoxicity. EPO was injected at doses of 2500 and 5000 IU/kg seven days after the last METH administration (ip). Morris water maze test was performed following EPO injection (1 day after the last dose) to assess spatial memory. The brains were removed after the behavioral test, biochemical evaluations and immunohistochemistry (caspase-3 and GFAP) was performed. RESULTS: The results showed that EPO treatment significantly improved spatial memory impairment (P < 0.01), compared to the METH group, EPO was a significant reduction in malondialdehyde and TNF-α (P < 0.01), as well as an increase in superoxide dismutase (P < 0.05) and glutathione-PX (P < 0.01). Furthermore, EPO treatment significantly reduced the number of GFAP positive cells (P < 0.01) and caspase 3 (P < 0.001) in the hippocampus (CA1 region). CONCLUSIONS: The study findings suggested that EPO may have great neuroprotective effects on METH neurotoxicity due to its anti-inflammatory, antioxidant, and antiapoptotic properties.

Lapse and Relapse Rates in Narcotics Anonymous versus Methadone Maintenance Treatment: A 12-Month Prospective Study.

Objective: The present study aimed to compare lapse and relapse-free survival between patients treated in Narcotics Anonymous (NA) groups and Methadone Maintenance Treatment (MMT) centers and to determine the relationship between social support scale and treatment outcome. Method: This study was a prospective, 12-month cohort study using the random sampling method to select 100 newcomer patients treated by the NA Association as well as 100 patients in MMT centers. The data were collected using a demographic questionnaire and Social Support Appraisals (SSA) scale at the onset of the study along with follow-up phone calls every other week. Results: All participants were male, aged between 18 and 65 with a mean (SD) age of 38.98 (± 10.85) years. Prevalence of relapse in 12 months was 60.5%. The lapses in the MMT group and relapses in the NA group were significantly higher (P < 0.001). The younger patients with lower levels of education are at greater risk of lapse/relapse. The mean score of SSA was significantly higher in the MMT group than the NA group in all subscales, including friends, family, and the others' support (P < 0.001). The mean scores of SSA subscales for the participants without relapse in the NA group was significantly higher in comparison to the MMT group. Conclusion: Detection of factors related to drug abuse relapse/lapse may help addiction therapists to identify drug abuse patients with lapse/relapse and to develop treatment and policy guidelines to prevent relapse in addiction recovery.

Antiproliferative properties of Turmerone on Leishmania major: Modes of action confirmed by antioxidative and immunomodulatory roles.

Treatment of leishmaniasis by conventional synthetic compounds has faced a serious challenge worldwide. This study was performed to evaluate the effect and modes of action of aromatic Turmerone on the Leishmania major intra-macrophage amastigotes, the causative agent of zoonotic cutaneous leishmaniasis in the Old World. In the findings, the mean numbers of L. major amastigotes in macrophages were significantly decreased in exposure to Turmerone plus meglumine antimoniate (Glucantime®; MA) than MA alone, especially at 50 µg/mL. In addition, Turmerone demonstrated no cytotoxicity as the selectivity index (SI) was 21.1; while it induced significant apoptosis in a dose-dependent manner on L. major promastigotes. In silico molecular docking analyses indicated an affinity of Turmerone to IL-12, with the MolDock score of - 96.8 kcal/mol; which may explain the increased levels of Th1 cytokines and decreased level of IL-10. The main mechanism of action is more likely associated with stimulating a powerful antioxidant and promoting the immunomodulatory roles in the killing of the target organism.

Apelin-13 attenuates spatial memory impairment by anti-oxidative, anti-apoptosis, and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus.

It has been shown that alcohol consumption by pregnant women can have detrimental effects on the developing fetus and lead to fetal alcohol spectrum disorders (FASD). Exposure to alcohol in rat pups during this period causes long-term changes in the structure of the animal's hippocampus, leading to impaired hippocampal-related brain functions such as navigation tasks and spatial memory. Apelin-13, a principal neuropeptide with inhibitory effects on neuroinflammation and brain oxidative stress production, has beneficial properties on memory impairment and neuronal injury. The protective effects of apelin-13 have been evaluated on ethanol-related neurotoxicity in the hippocampus of rat pups. Rat pups from 2 until 10 postnatal day, similar to the third trimester of pregnancy in humans, were intubated total daily dose of ethanol (5/27 g/kg/day). Immediately after intubation, 25 and 50 µg/ kg of apelin-13 was injected subcutaneously. By using Morris water maze task, the hippocampus- dependent memory and spatial learning were evaluated 36 days after birth. Then, Immunohistochemical staining was done to determine the levels of GFAP and caspase-3. ELISA assay was also performed to measure both TNF-α and antioxidant enzymes levels. The current study demonstrates that administration of apelin-13 attenuates spatial memory impairment significantly (P < 0.001). After ethanol neurotoxicity, apelin-13 could also increase the catalase level (P < 0.001), activity of total superoxide dismutase as well as glutathione concentration noticeably (P < 0.05). Other impacts of it could be mentioned as attenuating TNF-α production and also preventing lipid peroxidation (P < 0.001). In addition, the results showed that the level of GFAP as a neuroinflammation factor and the number of active caspase-3 positive cells can be decreased by apelin-13 (P < 0.01). Regarding the protective effects of apelin-13 against ethanol-induced neurotoxicity, it is a promising therapeutic choice for FASD; but more studies are needed.

Effects of berberine hydrochloride on methamphetamine-induced anxiety behaviors and relapse in rats.

OBJECTIVES: This research aimed at evaluating the effect of berberine hydrochloride on anxiety-related behaviors induced by methamphetamine (METH) in rats, assessing relapse and neuroprotective effects. MATERIALS AND METHODS: 27 male Wistar rats were randomly assigned into groups of Control, METH-withdrawal (METH addiction and subsequent withdrawal), and METH addiction with berberine hydrochloride oral treatment (100 mg/kg/per day) during the three weeks of withdrawal. Two groups received inhaled METH self-administration for two weeks (up to 10 mg/kg). The elevated plus maze (EPM) test and open field test (OFT) were carried out one day after the last berberine treatment and relapse was assessed by conditional place preference (CPP) test. TUNEL assay and immunofluorescence staining for NF-κB, TLR4, Sirt1, and α-actin expression in the hippocampus were tested. RESULTS: After 3 weeks withdrawal, berberine hydrochloride decreased locomotor activity and reduced anxiety-related behaviors in comparison with the METH-withdrawal group (P<0.001). The obtained results from CPP showed that berberine significantly reduced relapse (P<0.01). Significantly decrease in activation of TLR4, Sirt1, and α-actin in METH-withdrawal group was found and the percentage of TLR4, Sirt1, and α-actin improved in berberine-treated group (P<0.001). A significant activity rise of NF-κB of cells in the METH-withdrawal group was detected compared to berberine-treated and control groups (P<0.001). CONCLUSION: Treatment with berberine hydrochloride via modulating neuroinflammation may be considered as a potential new medication for the treatment of METH addiction and relapse. The histological assays supported the neuroprotective effects of berberine in the hippocampus.

Hydrogen Sulfide Attenuates the Neurotoxicity in the Animal Model of Fetal Alcohol Spectrum Disorders.

Fetal alcohol spectrum disorder (FASD), which is caused by prenatal alcohol exposure, can result in cell death in specific brain regions. Alcohol-induced neurocognitive defects offspring's are included with activation of oxidative-inflammatory cascade followed with wide apoptotic neurodegeneration in many brain's regions such as hippocampus. According to the latest studies, H2S (hydrogen sulfide) can protect neuronal cells via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms in different animal models. Therefore, we aimed to evaluate the protective effects of H2S on ethanol-induced neuroinflammation and neuronal apoptosis in pup hippocampus with postnatal alcohol exposure. Administration of ethanol (5.27 g/kg) in milk solution (27.8 mL/kg) for each rat pups was performed through intragastric intubation on 2 to 10 postnatal days and NaHS as H2S donor (1 mg/kg) was injected on similar time, subcutaneously. For examining the antioxidant and anti-inflammatory effects, ELISA assay was performed to determine the levels of TNF-α, IL1ß, and antioxidant enzymes. Immunohistochemical staining was performed to evaluate the expression levels of GFAP and caspase-3 also Nissl staining was done for necrotic cell death evaluation. H2S treatment could significantly increase the activity of total superoxide dismutase, catalase, and glutathione (P < 0.05). It also decreased the levels of TNF-α, IL1ß, and malondialdehyde, compared with the ethanol group (P < 0.05). Moreover, the number of hippocampal caspase-3, GFAP-positive cells, and necrotic cells death reduced in the H2S group (P < 0.01). Based on the findings, H2S can inhibit apoptotic signaling that is mediated by the oxidative-inflammatory cascade following ethanol exposure of rat pups on postnatal period.

A Review of the Historical Evolutionary Process of Dry and Water Maze Tests in Rodents.

This research provides an overview of the historical advances of the maze tests that are widely used to assess the cognitive impairments in rodents. Particularly, this study focuses on the issue of learning and memory behavioral tests, including dry and water mazes. Several types of mazes have been used in this setting, but their real advantages and applications depend on the type selected by the researcher. We answered some of the basic questions that any interested researcher in such studies may be faced with. The reviewed topics are as follows: the definition of maze learning, the role of the memory in the maze learning, the differences between several types of mazes, and foremost the rationale behind the maze constructions and designs.

Hydrogen sulfide improves spatial memory impairment via increases of BDNF expression and hippocampal neurogenesis following early postnatal alcohol exposure.

According to experimental and clinical findings, fetal brain development may be interrupted by maternal alcohol consumption during pregnancy. Adult hippocampal neurogenesis is thought to play a role in cognition function (i.e. learning and memory). Recent evidence suggests that ethanol administration causes major apoptotic neurodegeneration in many regions of the rats' developing brain during the synaptogenesis period. Based on the recent studies, H2S improve learning and memory via increased neurogenesis and antiapoptotic mechanisms in different animal models. In this study, we aimed to evaluate the protective effects of hydrogen sulfide on alcohol-induced memory impairment, hippocampus neurogenesis and neuronal apoptosis in rat pups with postnatal ethanol exposure. Administration of ethanol to male rat pups was performed through intragastric intubation on postnatal days 2-10. The pups were administered 1 mg/kg of NaHS (H2S donor) on postnatal days 2-10. For examining the spatial memory, Morris water maze test was carried out 36 days after birth. Following the behavioral test, immunohistochemical staining was performed to evaluate the expression levels of BrdU, BDNF and Apoptotic cell death was detected by TUNEL staining. Hydrogen sulfide (H2S) treatment could significantly improve spatial memory impairment (P < 0.05) and significantly increase the expression of BrdU and BDNF in dentate gyrus area (P < 0.05). It also decreased positive TUNEL cells, compared with the ethanol group (P < 0.01). Based on the findings, H2S makes significant neuroprotective effects on Ethanol neurotoxicity due to its neurogenesis and anti-apoptotic activity.

Sulfur dioxide reduces hippocampal cell death and improves learning and memory deficits in a rat model of transient global ischemia/reperfusion.

OBJECTIVES: According to recent the findings, sulfur dioxide (SO2) is produced by the cardiovascular system, influencing some major biological processes. Based on previous research, SO2 exhibits antioxidant effects and inhibits apoptosis following cardiac ischemia/reperfusion. Therefore, the objective of the current study was to examine the neuroprotective impact of SO2 following global cerebral ischemia/reperfusion (I/R). MATERIALS AND METHODS: Forty-eight male Wistar rats that weighed 260-300 g, were randomly allocated into 4 groups: sham group (n=12), I/R group (n=12), and I/R+SO2 groups (NaHSO3 and Na2SO3; 1:3 ratio; 5 and 10 µg/kg, respectively; for 3 days, n=12). Cerebral ischemia model was prepared by occlusion of both common carotid arteries for 20 min. Saline as a vehicle and SO2 donor at doses 5 µg/kg (intraperitoneally) were injected for 3 days after reperfusion. Four days after ischemia, the passive avoidance memory test was carried out in four groups, and after behavioral assessment, necrosis, apoptosis, and antioxidant enzyme analysis were carried out. RESULTS: O2 treatment could significantly improve memory impairments in rats with cerebral ischemia/reperfusion (I/R) (P<0.05). An increase in both superoxide dismutase and glutathione and a reduction in malondialdehyde were reported in the SO2 group versus the ischemic group (P<0.05). Moreover, SO2 could significantly decrease necrotic and apoptotic cells in the CA1 region (P<0.01). CONCLUSION: According to the findings, SO2 exerts significant neuroprotective effects on cerebral I/R due to its antioxidant activity.

Distribution of genes encoding virulence factors and multilocus variable-number tandem-repeat analysis (MLVA) of entero-aggregative Escherichia coli (EAEC) isolated in Iran from patients with diarrhoea.

PURPOSE: Entero-aggregative Escherichia coli (EAEC) is one of the main causes of diarrhoea worldwide. Several virulence factors have been identified in EAEC. This study was conducted to investigate the distribution of virulence factor genes in EAEC strains isolated in Iran from children with diarrhoea, as well as the genetic similarity of these isolates. METHODOLOGY: A total of 37 EAEC isolates were tested for the presence of 11 virulence genes by PCR, and the genetic relatedness of these strains was further determined by multilocus variable-number tandem-repeat analysis (MLVA). RESULTS: All EAEC isolates were typical EAEC. pic, set1A and set1B were the most prevalent genes, detected in 54.1 % of the isolates, followed by sat (43.2 %), astA (32.4 %), pet (24.3 %), agg4A (24.3 %), sepA (18.9 %), agg3A (13.5 %), sigA (8.1 %), aggA (8.1 %) and aafA (5.4 %). Using MLVA, the 37 isolates were divided into 32 types and classified into five clonal complexes. CONCLUSION: This study showed that EAEC is a heterogeneous group of E. coli possessing a broad range of virulence factors. There was no notable association between MLVA patterns and virulence profiles.

Results of Activity of Anonymous Alcoholic Association in Iran.

BACKGROUND: Alcoholics Anonymous (AA) is the largest non-governmental organization (NGO) for alcoholics in the world. During the recent decades, Iran has suffered from alcohol abuse and its consequences. Alcoholism is a taboo subject in Iran and there are few studies in this area. This is the first study in Iran to investigate the results of the activity of anonymous alcoholics. METHODS: Data were collected from the improved members of the AA in Iran (n = 6197). FINDINGS: The obtained results included members' demographic characteristics, age of sobriety, average attendance in weekly meetings, status of the sponsor, status of relapse, and the way of entering each member into AA groups. CONCLUSION: The activity of the AA in Iran is facing limitations and obstacles. The number of individuals with sobriety age above 20 years is not available because of the short-age activity of the AA in Iran. The number of men using this program is higher compared to women. Most members are individuals aging 31 to 40 years who are considered active members of the society.