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Bipolar disorder (BD) is a chronic psychiatric illness. Concentrations of inflammatory cytokines are increased in BD. Supplementation with probiotics has shown promising effects in reducing inflammation and producing improvement in clinical symptoms in some psychiatric disorders. Therefore, we designed a clinical trial to assess the effects of adjunctive probiotics on markers of inflammation and oxidative stress in patients with BD.In this 8-week, double-blind, randomized study, 38 patients suffering from BD type I were given a probiotic or placebo capsule each day. Serum levels of interleukin-6 (IL-6), as the primary outcome measure, and of interleukin-10 (IL-10), tumor necrosis factor-α, and malondialdehyde, as the secondary outcome measures, were obtained before and after the intervention.At the end of the study, the 2 groups showed no significant or clinically meaningful differences in the serum concentrations of IL-6 [Hedge g=0.02, 95% confidence interval (CI): -0.6; 0.64, P=0.936], tumor necrosis factor-α (Hedge g=-0.2, 95% CI: -0.82; 0.42, P=0.554), IL-10 (Hedge g=-0.072, 95% CI: -0.071; 0.56, P=0.827), and malondialdehyde (Hedge g=0.27, 95% CI: -0.37; 0.91, P=0.423).This study did not find any significant or conclusive effects of probiotics supplementation on markers of inflammation and oxidative stress in patients with BD. Further studies are needed before a conclusion can be drawn about the efficacy of probiotics in the management of BD.

Drug-induced stuttering (DIS) is a type of neurogenic stuttering (NS). Although DIS has not been reported as frequently as other cases of NS in the literature, it is not a negligible adverse drug reaction (ADR) which can significantly affect the quality of life if not treated. This literature review aims to evaluate the epidemiological and clinical characteristics of DIS and suggests some pathophysiological mechanisms for this ADR. Relevant English-language reports in Google Scholar, PubMed, Web of Science, and Scopus were identified and assessed without time restriction. Finally, a total of 62 reports were included. Twenty-seven drugs caused 86 episodes of stuttering in 82 cases. The most episodes of DIS were related to antipsychotic drugs (57%), mostly including clozapine, followed by central nervous system agents (11.6%) and anticonvulsant drugs (9.3%). The majority of the cases were male and between the ages of 31 and 40 years. Repetitions were the most frequent core manifestations of DIS. In 55.8% of the episodes of DIS, the offending drug was withdrawn to manage stuttering, which resulted in significant improvement or complete relief of stuttering in all cases. Based on the suggested pathophysiological mechanisms for developmental stuttering and neurotransmitters dysfunctions involved in speech dysfluency, it seems that the abnormalities of several neurotransmitters, especially dopamine and glutamate, in different circuits and areas of the brain, including cortico-basal ganglia-thalamocortical loop and white matter fiber tracts, may be engaged in the pathogenesis of DIS.

Background: the aim of this study was the isolation of phages able to lyse some strains of MDR-K. pneumoniae (named vB_Kp1 and vB_Kp2) and E. aerogenes (named vB_Ea1) from swages. Materials and Methods: Different Klebsiella pneumoniae and Enterobacter aerogenesis strains isolated from clinical specimens (January to September 2018) in three Hospitals in Amol, (Mazandaran, Iran). Kirby Bauer’s disc diffusion method was used for determination of resistance profiles of these isolates using different antibiotics. The resistant strains to multi tested antibiotics (MDR) were selected to investigate the effect of isolated phages from wastewater and hospital sewage. Presence of phage investigated by plaque formation and after enriching and concentrating the isolated bacteriophages and staining the samples, a transmitting electron microscope (TEM) was used to observe the morphology of the bacteriophages. Phage identification tests including host range and One-step growth were performed. Results: TEM analysis revealed that tree phages have an icosahedral capsid and long contractile tail. Therefore, they are a member of the Myoviridae family. Phages were able to lyse 14 (56%) of the 25 strains of multidrug-resistant bacteria isolated. The one-step growth curve showed large burst sizes and short latent times. Conclusions: The formation of clear plaques shows the high lyse power of phages, so they have good potential for further analysis for clinical use as a therapeutic agent in the future.

Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property.

A series of novel metronidazole aryloxy, carboxy and azole derivatives has been synthesized and their cytotoxic activities on three cancer cell lines were evaluated by MTT assay. Compounds 4m, 4l and 4d showed the most potent cytotoxic activity (IC50s less than 100 µg/mL). Apoptosis was also detected for these compounds by flow cytometry. Docking studies were performed in order to propose the probable target protein. In the next step, molecular dynamics simulation was carried out on the proposed target protein, focal adhesion kinase (FAK, PDB code: 2ETM ), bound to compound 4m. As, 4m showed a potent cytotoxic activity and an acceptable apoptotic effect, it can be a potential anticancer candidate that may work through inhibition of FAK.

Background and Objectives: Multi-drug-resistant Enterobacter aerogenes is associated with various infectious diseases that cannot be easily treated by antibiotics. However, bacteriophages have potential therapeutic applications in the control of multi-drug-resistant bacteria. In this study, we aimed to isolate and characterize of a lytic bacteriophage that can lyse specifically the multi-drug-resistant (MDR) E. aerogenes. Materials and Methods: Lytic bacteriophage was isolated from Qaem hospital wastewater and characterized morphologically and genetically. Next-generation sequencing was used to complete genome analysis of the isolated bacteriophage. Results: Based on the transmission electron microscopy feature, the isolated bacteriophage (vB-Ea-5) belongs to the family Myoviridae. vB-Ea-5 had a latent period of 25 minutes, a burst size of 13 PFU/ml, and a burst time of 40 min. Genome sequencing revealed that vB-Ea-5 has a 135324 bp genome with 41.41% GC content. The vB-Ea-5 genome codes 212 ORFs 90 of which were categorized into several functional classes such as DNA replication and modification, transcriptional regulation, packaging, structural proteins, and a host lysis protein (Holin). No antibiotic resistance and toxin genes were detected in the genome. SDS-PAGE of vB-Ea-5 proteins exhibited three major and four minor bands with a molecular weight ranging from 18 to 50 kD. Conclusion: Our study suggests vB-Ea-5 as a potential candidate for phage therapy against MDR E. aerogenes infections.

Aim: The study aimed to investigate the relationship between the occurrence of Severe Early Childhood Caries (S-ECC) and breast milk lactose, in infants aged 12 to 24 months.Material and Methods: This cross-sectional descriptive-analytical study was carried out in April to July 2020 on 30 children aged 12 to 24 months with or without S-ECC who were solely breastfed Also, the mothers answered questions about their breastfeeding. After the child's dental visit, the mother was asked to express 10 to 20 ml of her milk as a sample and give it to the researchers. The samples were immediately kept at -4 ° C and then they were tested to lactose measurement. Finally, the test results were analyzed by SPSS 21 software. Results: The average amount of lactose in the breast milk of cases with S-ECC infant was 5.74g/100 ml, and the average amount of lactose in the breast milk of cases without S-ECC infant was 4.64g/100 ml. There was no significant difference in lactose concentration between the two groups (p=0/64). The average number of breastfeeding times in cases with S-ECC infants was 7.87 per day while in the healthy cases this was 7.33 per day. There was no significant difference between the numbers of breastfeeding times per day in the two groups.Conclusion: According to this study, the average level of lactose in the breast milk samples was lower than the average level of lactose in breast milk in other countries, and the amount of lactose in breast milk of children with S-ECC was slightly higher than the amount of lactose in breast milk in children with healthy teeth.

Aim: The study aimed to investigate the relationship between occurrence of Severe Early Childhood Caries (S-ECC) and breast milk lactose, in infants aged 12 to 24 months.Material and Methods: This cross-sectional descriptive-analytical study performed on 30 children aged 12 to 24 months with or without S-ECC who were solely breastfed, and mothers answered questions about their breastfeeding. After the child's dental visit, the mother was asked to express 10 to 20 ml of her milk as a sample and give it to the researchers. The samples were immediately kept at -4 ° C and then they were tested to lactose measurement. Finally, the test results were analyzed by SPSS 21 software. Results: the average amount of lactose in the breast milk sof cases with S-ECC infant was 5.74g/100 ml and the average amount of lactose in the breast milk of cases without S-ECC infant was 4.64g/100 ml. There was no significant difference in lactose concentration between the two groups (p=0/64). The average number of breastfeeding times in cases with S-ECC infants was 7.87 per day while in the healthy cases this was 7.33 per day. There was no significant difference between the numbers of breastfeeding times per day in two groups.Conclusion: According to this study, the average level of lactose in the breast milk samples was lower than the average level of lactose in breast milk in other countries and the amount of lactose in breast milk of children with S-ECC was slightly higher than the amount of lactose in breast milk in children with healthy teeth.

E. coli O157:H7 is a foodborne pathogen mostly related to consumption of meat and vegetables. Although using antibiotics is not recommended in treatment of infections caused by this pathogen, antibiotic resistant isolates are reported. This has encouraged researchers to find alternative methods to treat and effective approaches to prevent the E. coli O157:H7 infections. Phage therapy is one of the techniques with therapeutic and biocontrol applications. The aim of this study was to find effective phages capable of lysing this pathogen. Twenty samples were searched for phages against E. coli O157:H7. The host range of the isolated phages was determined. The phages with broader host range were selected for structural study. The stability in different temperature and pH values were also performed. Phages kmuOR and kmuGH could lyse two strain of E. coli O157:H7, some clinical non-O157 E. coli strains, and a strain of Shigella flexneri, another enteric pathogen. Transmission electronic micrograph revealed that both phages belong to Myoviridae family. The two phages were resistant to pH 3 to 9.5 and temperatures 4-50°C and able to prevent the growth of E. coli O157:H7 in LB medium. Further study can prove the suitability of these phages as biocontrol or phage therapy agents.

Objective There are some reports of the effect of the gut microbiota on the central nervous system. The aim of this study was to find out the effect of probiotics on pentylenetetrazol (PTZ)-induced convulsions in mice. Methods The mice were pretreated with probiotic powder (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum) suspended in normal saline by intragastric gavage (IG-gavage) for 14 (group 1) or 28 (group 2) days prior to injection of PTZ (90 mg/kg, intraperitoneally). Diazepam (DZP, 1 mg/kg, intraperitoneally) was used as the reference drug. The latency and duration of induced convulsion, as well as mortality protection percentage were recorded 30 min after PTZ injection. For the next step, flumazenil (FLZ) was used to block the effect of DZP. Results Pretreatment with probiotics for 14 or 28 days had not a significant effect on the latency and duration of seizures induced by PTZ. Neither seizure nor mortality was observed in co-administration of probiotics with DZP. FLZ pretreatment decreased the DZP-induced seizure latency; however, FLZ could not have such an effect in probiotic and DZP group. Conclusion Probiotics alone did not show anticonvulsant effects, but enhanced the anticonvulsant effect of DZP; this suggests the involvement of GABAergic system.

Phage therapy is an old method of combating bacterial pathogens that has recently been taken into consideration due to the alarming spread of antibiotic resistance. Escherichia coli O157:H7 is a foodborne pathogen that causes hemorrhagic colitis and life-threatening Hemolytic Uremic Syndrome (HUS). There are several studies on isolation of specific phages against E. coli O157:H7 and more than 60 specific phages have been published so far. Although in vitro experiments have been successful in elimination or reduction of E. coli O157:H7numbers, in vivo experiments have not been as promising. This may be due to escape of bacteria to locations where phages have difficulties to enter or due to the adverse conditions in the gastrointestinal tract that affect phage viability and proliferation. To get around the latter obstacle, an alternative phage delivery method such as polymer microencapsulation should be tried. While the present time results are not very encouraging the work should be continued as more efficient phage treatment regimens might be found in future.

BackgroundAcute otitis media (AOM) is very common in children. In spite of spontaneously relief, some cases suffer from the recurrence and other complications occurring after AOM. Animal studies have proved that persistence of leukotrienes in the middle ear may play a role in the development of AOM. Based on this statement, treatment with leukotriene modifiers may be effective in the treatment of OM. The aim of this study was to examine the effect of adjunction of montelukast to antibacterial agents in treatment of AOM.Materials and MethodsOne hundred patients aged 2-6 years were randomly divided into two groups. One of the groups (53%) were treated with "amoxicillin alone", 80-90 mg/kg amoxicillin for 10 days, and the other group (47%), received "amoxicillin and montelukast" 5 mg per day orally for 10 days. Patients were evaluated for resolution and complications of AOM at 2 post enrollment visits (days 2-4 and 10-14).ResultsThe patient followed-up for one month and results showed that, treatment with montelukast had beneficial effects on resolution of AOM. In monotherapy (amoxicillin alone) group, 66% of patients and in the montelukast (amoxicillin and montelukast) group, 85.1% were treated.ConclusionIn this study, the montelukast receiving group showed a better response to treatment. Based on this and previous studies, it is recommended to consider the role of inflammatory mediators in AOM. Prescribing montelukast and other leukotriene receptor antagonists may have benefits for the patients.

Minocycline as a member of the tetracycline family is a lipophilic broad-spectrum antibiotic, which can display some non-antibiotic properties such as antioxidant, antiapoptosis, neuroprotection and modulation of pharmacological traits of drugs of abuse (ie, reward, sensitization and/or analgesia). Thus, the aim of the present study was to investigate the effect of intracerebroventricular (ICV) injection of minocycline on morphine-induced memory impairment and motor function in male Wistar rats. The behavioural responses were measured by a passive avoidance test for evaluating memory, and in the open field for studying motor function. Furthermore, the expression of Phospho-cAMP response element-binding protein (P-CREB) and c-Fos were assessed using immunohistochemistry in the dorsal hippocampus and basolateral amygdala (BLA). Our results showed that morphine dose-dependently impairs memory consolidation, but not motor function. Maximum effect was achieved with morphine at dose of 5 mg/kg. Pretreatment with ICV injection of minocycline (50 μg/rat) prevented morphine-induced memory impairment, but there was no effect on motor function. The results of immunohistochemistry analysis demonstrated that morphine decreased expression of P-CREB positive cells compared to saline control group in the BLA, but not in the dorsal hippocampus. On the other hand, pretreatment of animals with ICV injection of minocycline increased the expression of P-CREB in both brain areas. Moreover, there was no significant change in the expression of c-Fos positive cells in above-mentioned regions. In summary, our results indicated that pretreatment with ICV injection of minocycline prevented morphine-induced memory impairment and increased P-CREB expression in the dorsal hippocampus and BLA, which may explain its memory improvement property.

Three-component reaction of 3-hydroxy-4H-chromen-4-one, aromatic aldehydes and malononitrile or ethyl cyanoacetate in EtOH, at reflux and in the presence of catalytic amounts of nanosized MgO has been used for the synthesis of dihydropyrano[3,2-b]chromene derivatives. A number of advantages are associated with this method such as, easy monitoring of reaction progress, convenient workup procedure and high yields. The antiproliferative effects of these compounds were tested by MTT assay on six cell lines; five cancerous (Caco-2, A549, MCF-7, HT1080, and U87) and one normal (3T3). The results revealed that some of these compounds had cytotoxicity against tested cell lines especially against Caco-2 (colorectal) cell line.

Background Active learning methods are strategies used by most universities worldwide to enhance the problem-solving ability and develop critical thinking in students. Team-based learning (TBL) is one of these methods, in which students study the lesson prior to discussion. At the beginning of the session, the individual readiness assurance test (iRAT) is given to students, and then they answer the same questions through discussion in a team. Finally, problems are resolved by the teacher and results are given to students. Methods In the current study, 30 pharmacology students were randomly assigned to two groups of 16 and 14 subjects. The educational content of pharmaceutical biotechnology was given to the 16- and 14-subject groups using traditional lecturing and TBL methods, respectively. Finally, both groups were assessed and compared based on a same method. Results The average scores of the lecturing and TBL groups were 6.77 ± 1.97 and 8.32 ± 2.65 out of 13.75, respectively (6.25 scores belonged to class activities, which were not included in comparisons). No significant difference was observed between the mean score of groups (P = 0.07), although the difference was very close to significant, which can be attributed to the current study’s small sample size. One subject in the TBL group and six in the lecturing group failed to pass the course; the difference between the groups in this regard was noticeable. Conclusions Although results of the current study showed no significant superiority of TBL over the lecturing method, most students were satisfied with the TBL method. Hence, it is recommended to employ this method with freshmen.

Bacteriophages are considered as promising biological agents for the control of infectious diseases. Sequencing of their genomes can ascertain the absence of antibiotic resistance, toxin or virulence genes. The anti-O157 : H7 coliphage, PhaxI, was isolated from a sewage sample in Iran. Morphological studies by transmission electron microscopy showed that it has an icosahedral capsid of 85–86 nm and a contractile tail of 115×15 nm. PhaxI contains dsDNA composed of 156 628 nt with a G+C content of 44.5 mol% that encodes 209 putative proteins. In MS analysis of phage particles, 92 structural proteins were identified. PhaxI lyses Escherichia coli O157 : H7 in Luria-Bertani medium and milk, has an eclipse period of 20 min and a latent period of 40 min, and has a burst size of about 420 particles per cell. PhaxI is a member of the genus ‘Viunalikevirus’ of the family Myoviridae and is specific for E. coli O157 : H7.