Examining the performance of responding to the Khoy earthquake 2022, challenges, strengths, and lessons learned: thematic analysis.

OBJECTIVE: Disasters in developing countries result in higher human and financial losses compared to global standards, with the death rate being 12 times higher than that of developed countries. Many experts attribute the failures in disaster management to the lack of a system for documenting and analyzing disaster management functions and not leveraging the experiences and lessons learned. This study employed a qualitative data collection approach, utilizing semi-structured interviews with managers, deputies, members of operational teams, and individuals affected by the disaster in the area. This research aims to explore the challenges, strengths, and lessons learned from the response to the Khoy earthquake in Iran. RESULTS: After conducting 40 interviews and achieving data saturation, we extracted experiences and lessons learned to investigate the performance of responsible organizations in the 2022 Khoy earthquake. The obtained data were categorized into 8 categories and 39 sub-categories. These categories encompassed warning and calling forces, disaster assessment, disaster commanding, emergency housing, supply and distribution of items, organization, and guidance of public participation and charities, psychological support, logistics operations, monitoring, evaluation, documentation, information dissemination, and media management. Planners and operational managers can use the findings to review and revise their action and prevention plans.

Mechanical, structural, and morphological differences in the iliac arteries.

Iliac arteries play a crucial role in peripheral blood circulation. They are susceptible to various diseases, including aneurysms and atherosclerosis. Structure, material properties, and biomechanical forces acting on different regions of the iliac vasculature may contribute to the localization and progression of these pathologies. We examined 33 arterial specimens from common iliac (CI), external iliac (EI), and internal iliac (II) arteries obtained from 11 human donors (62 ± 12 years). We conducted morphometric, mechanical, and structural analyses using planar biaxial tests, constitutive modeling, and bi-directional histology on transverse and axial sections. The iliac arteries exhibited increased tortuosity and varying disease distribution with age. CI and II arteries displayed non-uniform age-related disease progression around their circumference, while EI remained healthy even in older individuals. Trends in load-free and stress-free thickness varied along the iliac vasculature. Longitudinally, EI exhibited the highest compliance compared to other iliac vessels. In contrast, CI was stiffest longitudinally, and EI was the stiffest circumferentially. Material parameters for all iliac vessels are reported for four common constitutive relations. Elastin near the internal elastic lamina displayed greater waviness in EI and II compared to CI. Also, EI had the least glycosaminoglycans (GAGs) and the highest elastin content. Our findings highlight variations in the morphological, mechanical, and structural properties of iliac arteries along their length. This data can inform vascular disease development and computational studies, and guide the development of biomimetic repair materials and devices tailored to specific iliac locations, improving vascular repair strategies.

Mechanical, structural, and physiologic differences between above and below-knee human arteries.

Peripheral Artery Disease (PAD) affects the lower extremities and frequently results in poor clinical outcomes, especially in the vessels below the knee. Understanding the biomechanical and structural characteristics of these arteries is important for improving treatment efficacy, but mechanical and structural data on tibial vessels remain limited. We compared the superficial femoral (SFA) and popliteal (PA) arteries that comprise the above-knee femoropopliteal (FPA) segment to the infrapopliteal (IPA) anterior tibial (AT), posterior tibial (PT), and fibular (FA) arteries from the same 15 human subjects (average age 52, range 42-67 years, 87 % male). Vessels were imaged using µCT, evaluated with biaxial mechanical testing and constitutive modeling, and assessed for elastin, collagen, smooth muscle cells (SMCs), and glycosaminoglycans (GAGs). IPAs were more often diseased or calcified compared to the FPAs. They were also twice smaller, 53 % thinner, and significantly stiffer than the FPA longitudinally, but not circumferentially. IPAs experienced 48 % higher physiologic longitudinal stresses (62 kPa) but 27 % lower circumferential stresses (24 kPa) and similar cardiac cycle stretch of <1.02 compared to the FPA. IPAs had lower longitudinal pre-stretch (1.12) than the FPAs (1.29), but there were no differences in the stored elastic energy during pulsation. The physiologic circumferential stiffness was similar in the above and below-knee arteries (718 kPa vs 754 kPa). Structurally, IPAs had less elastin, collagen, and GAGs than the FPA, but maintained similar SMC content. Our findings contribute to a better understanding of segment-specific human lower extremity artery biomechanics and may inform the development of better medical devices for PAD treatment. STATEMENT OF SIGNIFICANCE: Peripheral Artery Disease (PAD) in the lower extremity arteries exhibits distinct characteristics and results in different clinical outcomes when treating arteries above and below the knee. However, their mechanical, structural, and physiologic differences are poorly understood. Our study compared above- and below-knee arteries from the same middle-aged human subjects and demonstrated distinct differences in size, structure, and mechanical properties, leading to variations in their physiological behavior. These insights could pave the way for creating location-specific medical devices and treatments for PAD, offering a more effective approach to its management. Our findings provide new, important perspectives for clinicians, researchers, and medical device developers interested in treating PAD in both above- and below-knee locations.

Variability in structure, morphology, and mechanical properties of the descending thoracic and infrarenal aorta around their circumference.

Aortic diseases, such as aneurysms, atherosclerosis, and dissections, demonstrate a preferential development and progression around the aortic circumference, resulting in a highly heterogeneous disease state around the circumference. Differences in the aorta's structural composition and mechanical properties may be partly responsible for this phenomenon. Our goal in this study was to analyze the mechanical and structural properties of the human aorta at its lateral, anterior, posterior, and medial quadrants in two regions prone to circumferentially inhomogeneous diseases, descending Thoracic Aorta (TA) and Infrarenal Aorta (IFR). Human aortas were obtained from 10 donors (64 ± 11 years) and dissected from their loose surrounding tissue. Mechanical properties were determined in all four quadrants of TA and IFR using planar biaxial testing and fitted to three common constitutive models. The structure of tissues was assessed using Movat Pentachrome stained histology slides. We observed that the anterior quadrant exhibited the greatest thickness, followed by the lateral region, in both the TA and IFR. In TA, the posterior wall appeared as the stiffest location in most samples, while in IFR, the anterior wall was the stiffest. We observed a higher glycosaminoglycans content in the lateral and posterior regions of the IFR. We found elastin density to be similar in TA lateral, anterior, and posterior quadrants, while in IFR, the anterior region demonstrated the highest elastin density. Despite significant variations between subjects, this study highlights the distinct morphometrical, mechanical, and structural properties between the quadrants of both TA and IFR.

Simvastatin improves learning and memory impairment via gut-brain axis regulation in an ovariectomized/D-galactose Alzheimer's rat model.

AIM: Alzheimer's disease (AD) is the most prevalent form of dementia with multiple etiology and no effective remedy. Statins are a group of medicines that are basically used to lower cholesterol. However, several studies have recently done to assess the potential relationship between statins use and dementia but presented controversial results. METHODS: In this study, using ovariectomy and D-galactose injection, a model of AD was induced in female rats, and then the protective effects of oral administration of simvastatin were investigated. shuttle box and Y-maze tests were done to assess the animals' learning and memory performance. Using GC-MC, ELISA, Immunohistochemistry and tissue staining techniques, changes in the amount of short-chain fatty acids (SCFAs), plasma and hippocampus neuroinflammatory markers and histological changes in the intestine and hippocampus were assessed in sham, disease and treatment groups. KEY FINDINGS: Oral administration of simvastatin improved the gut microbiome activity (increased the amount of SCFAs in fecal samples) and strengthened the tight junctions of intestinal cells. Moreover, simvastatin reduced the amount of TNF-α and IL-1ß in plasma and hippocampus. Also, cell death and Amyloid plaques notably decreased in the simvastatin-treated hippocampal tissue. All these physiological changes led to better performance in behavioral tasks in the treatment group in comparison to the disease group. SIGNIFICANCE: These findings provide evidence that simvastatin may improve gut-brain axis followed by improvement in learning and memory via an anti-inflammatory effect.

Stb6 mediates stomatal immunity, photosynthetic functionality, and the antioxidant system during the Zymoseptoria tritici-wheat interaction.

This study offers new perspectives on the biochemical and physiological changes that occur in wheat following a gene-for-gene interaction with the fungal pathogen Zymoseptoria tritici. The Z. tritici isolate IPO323, carries AvrStb6, while ΔAvrStb6#33, lacks AvrStb6. The wheat cultivar (cv.) Shafir, bears the corresponding resistance gene Stb6. Inoculation of cv. Shafir with these isolates results in two contrasted phenotypes, offering a unique opportunity to study the immune response caused by the recognition of AvrStb6 by Stb6. We employed a variety of methodologies to dissect the physiological and biochemical events altered in cv. Shafir, as a result of the AvrStb6-Stb6 interaction. Comparative analysis of stomatal conductance demonstrated that AvrStb6-Stb6 mediates transient stomatal closures to restrict the penetration of Zymoseptoria tritici. Tracking photosynthetic functionality through chlorophyll fluorescence imaging analysis demonstrated that AvrStb6-Stb6 retains the functionality of photosynthesis apparatus by promoting Non-Photochemical Quenching (NPQ). Furthermore, the PlantCV image analysis tool was used to compare the H2O2 accumulation and incidence of cell death (2, 4, 8, 12, 16, and 21 dpi), over Z. tritici infection. Finally, our research shows that the AvrStb6-Stb6 interaction coordinates the expression and activity of antioxidant enzymes, both enzymatic and non-enzymatic, to counteract oxidative stress. In conclusion, the Stb6-AvrStb6 interaction in the Z. tritici-wheat pathosystem triggers transient stomatal closure and maintains photosynthesis while regulating oxidative stress.

Investigating Cognitive Functions in Methadone Users in Comparison with Methadone and Methamphetamine Users and Control Group.

Background: Cognitive impairment in drug users is a marker for predicting recurrence and poorer adherence to treatment. The purpose of this study was to compare the cognitive function in three groups of methadone users methadone maintenance treatment (MMT), compared to methadone and methamphetamine (MAMP) users (MMT + MAMP) and healthy people (control group). Methods: Three groups of 90 people including 30 users of MMT, 30 users of MMT + MAMP, and 30 healthy persons participated in this cross-sectional and purposeful study. The study was performed on outpatients of MMT Clinic of Psychiatric Hospital in Kerman, Iran. The demographic and related data questionnaire was filled out. In addition, Persian version of the Brief Assessment of Cognition in Schizophrenia (BACS) was used to assess cognitive function. Findings: The mean of total number of scores and all BACS subscales were significantly better in control group than the other two groups of patients. Moreover, not only the mean of total number of BACS was significantly different between two substance abuser groups, but also there was a significant difference between them on verbal memory, digit sequencing, and token motor test, with MMT + MAMP group performing worse than MMT group. Conclusion: Concomitant use of opioids and stimulant substance such as MAMP results in cumulative toxic effect of them on brain and cognitive functions.

Evaluation of the Effect of (S)-3,4-Dicarboxyphenylglycine as a Metabotropic Glutamate Receptors Subtype 8 Agonist on Thermal Nociception Following Central Neuropathic Pain.

STUDY DESIGN: In this study, we decided to change the activity of periaqueductal gray (PAG)'s metabotropic glutamate receptors subtype 8 (mGluR8) by means of its specific agonist, (S)-3,4-dicarboxyphenylglycine (DCPG), and by knock downing it with mGluR8 siRNA. We then evaluated the changes in animal pain threshold levels in the face of painful thermal stimuli (thermal hyperalgesia). PURPOSE: Although several mechanisms have been examined for central neuropathic pain, researchers have so far failed to find the precise mechanism for the development and progression of this type of pain. Hyperalgesia is one of the most important complications of central neuropathic pain and there is not a consensus among researchers about the exact cause of this complication. In this study, we investigated the effect of activation of the PAG region mGluR8 on the threshold of pain response to thermal noxious stimulus in rats and measured mGluR8 expression. OVERVIEW OF LITERATURE: Spinal cord injury (SCI) produces an decrease in mGluR2/3 expression in the injured and vehicle-treated groups compared to normal levels, APDC and L-AP4 treated groups had higher expression levels of mGluR2/3. These findings suggesting that the level of mGluR expression after SCI may modulate nociceptive responses. METHODS: Male Wistar rats were randomly assigned to five groups (n=10 per group). The clip compression injury model was used to induce chronic central neuropathic pain. Three weeks after SCI, DCPG, siRNA, or normal saline were administered to the intra-ventrolateral PAG region. Withdrawal threshold to the noxious thermal stimulus (e.g., heat hyperalgesia) was assessed through the tail-flick test. In order to assure involvement of this receptor, pain responses were compared with mice that received GRM8 siRNA. RESULTS: We found that the mGluR8 agonist DCPG increased lead to an increased expression of mGluR8 in the PAG region. We also found that SCI can decrease the threshold of response to painful thermal stimuli; however, activation of mGluR8 with DCPG agonist did not significantly improve the tail-flick response. CONCLUSIONS: The results revealed that activation of mGluR8 in PAG is not capable of improving the thermal hyperalgesia threshold. Based on the decreased expression of mGluR8 after SCI induced by clip compression injury and its significant increase after treatment of siRNA against mGluR8, this method might still hold promise as an effective treatment of neuropathic pain. It can be concluded that increased expression of mGluR8 is due to the fact that DCPG prevents the death of neurons that express these receptors.

Netrin-1 protects the SH-SY5Y cells against amyloid beta neurotoxicity through NF-κB/Nrf2 dependent mechanism.

Many evidence confirms that amyloid beta 1-42 fragment (Aß1-42) causes neuroinflammation, oxidative stress, and cell death, which are related to progressive memory loss, cognitive impairments and mental disorders that will lead to Alzheimer's disease (AD) progression. Netrin-1, as a member of the laminins, has been proved to inhibit apoptosis and inflammation outside of nervous system, in addition to having a vital role in morphogenesis and neurogenesis of neural system. This study was designed to assess the protective effects of netrin-1 in SH-SY5Y human neuroblastoma cell line exposed to Aß1-42 and to explore some mechanisms that underlie netrin-1 effects. Cultured SH-SY5Y neuroblast-like cells were treated with netrin-1 prior to Aß1-42 exposure and the effects were assessed by MTT and ELISA assay kits. Netrin- 1 pretreatment of Aß1-42-exposed SH-SY5Y human neuroblastoma cells attenuated Aß1-42 induced toxic effects, increased cell viability and partially restored levels of 3 inflammatory and oxidative stress biomarkers including: nuclear factor erythroid 2-like 2 (Nrf2), tumor necrosis factor alpha (TNFα) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB). Based on the findings of this study, netrin-1 represents a promising therapeutic bio agent to abrogate cellular inflammation and reactive oxygen species (ROS) activation induced by Aß1-42 in the SH-SY5Y cell model of AD.

The effect of periaqueductal gray's metabotropic glutamate receptor subtype 8 activation on locomotor function following spinal cord injury.

Background and aims The pathophysiology of spinal cord injury is very complex. One of the debilitating aspects of spinal cord injury in addition to pain is a defect in motor function below the lesion surface. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, on animal's locomotor functions in a model of compression spinal cord injury. Methods We used a contusion method (T6-T8) for induction of spinal cord injury. Male Wistar rats were randomly assigned to five equal groups (n = 10 per group). Clips compression injury model was used to induce spinal cord injury. Three weeks post injury DCPG, siRNA (small interfering Ribonucleic Acid) and normal saline (vehicle) were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Motor function, were assessed through BBB (Basso, Beattie, and Bresnahan Locomotor Rating Scale) and ladder walking test. In addition, the effects of DCPG on axonal regeneration in corticospinal tract were evaluated. Results We found that DCPG could improve motor function and axonal regeneration in corticospinal tract when compared to siRNA group. Conclusions The results revealed that activation of mGluR8 in PAG is capable to improve motor function and of axonal regeneration due to the inhibitory effect on glutamate transmission on the spinal cord surface and also the elimination of the deleterious effect of glutamate on the regeneration of the injured area as an excitatory neurotransmitter. Implications Our findings in this study showed that, more attention should be paid to glutamate and its receptors in spinal cord injury studies, whether at the spinal or cerebral level, especially in the field of motor function after spinal cord injury.

Protagonist Role of Opioidergic System on Post-Traumatic Stress Disorder and Associated Pain.

OBJECTIVE: Post-traumatic stress disorder (PTSD) and chronic pain often co-occur. Studies have shown an interaction between pain and PTSD. In this narrative review, we aim to support conducting comprehensive studies by describing PTSD, pain and determining whether opioidergic system, its agonist and antagonist manipulation could positively or negatively affect PTSD symptoms and concurrent pain. METHODS: Term searches was done in Google Scholar, Scopus, ScienceDirect, Web of Science and PubMed databases as well as hand searching in key resource journals from 1979-2019. RESULTS: There are a lot of contradictions and disputes when endogenous opioidergic system and opioidergic antagonist system are studied in PTSD patients. Exogenous morphine administration in PTSD patients can decrease the symptoms of PTSD but it doesn't have a pain reduction effect to an acceptable level. Beta-endorphin as an endogenous opioid is effective in pain reduction in the moment of events but after minutes to hours, the endorphins withdrawal syndrome leads to exaggerated intrusive thoughts and flashbacks of PTSD, which exacerbate the pain. It has also been shown that naloxone, as an opioidergic antagonist, can reduce or increase the PTSD symptoms and its associated pain. CONCLUSION: Data suggest different roles of opioidergic system and their antagonist in pain control and mood in PTSD. However, further investigations need to be done in order to reveal the role of endogenous opioidergic system and opioidergic antagonist system as a mediator in PTSD patients suffering from acute or chronic pain.

The inhibiting role of periaqueductal gray metabotropic glutamate receptor subtype 8 in a rat model of central neuropathic pain.

The pathophysiology of neuropathic pain is very complex. It involves several environmental and central mechanisms. In this study, we tried to assess the modulatory effect of (S)-3,4-Dicarboxyphenylglycine (DCPG), a metabotropic glutamate receptor subtype 8 (mGluR8) agonist, in a model of chronic central neuropathic pain in male rats. We used a spinal cord contusion method (T6-T8) for the induction of chronic central neuropathic pain.Male Wistar rats were randomly assigned to 5 equal groups (n = 10 per group). Clips compression injury model was used to induce chronic central neuropathic pain. Three weeks after spinal cord injury DCPG, siRNA and normal saline were administered intra-ventrolaterally to the periaqueductal gray (PAG) region. Paw withdrawal response to acetone (cold allodynia) was assessed through acetone test. In addition, the effects of DCPG on rostral ventromedial medulla (RVM) off-cells activity were evaluated with immunohistochemistry. mGluR8 expressions were also measured.We found that treatment with DCPG increased pain threshold in acetone test. In addition, immunohistochemical evaluation of RVM off-cells showed that DCPG increased the suppressive function of these cells.The results revealed that activation of mGluR8 in PAG is capable to improve pain threshold via modulation of RVM off-cells activity.Abbreviations SCI: spinal cord injury; DCPG: (S)-3,4-dicarboxyphenylglycine; PAG: periaqueductal gray; siRNA: small interfering ribonucleic acid; RVM: rostral ventromedial medulla; mGluR: metabotropic glutamate receptor.

Simultaneous intrathecal injection of muscimol and endomorphin-1 alleviates neuropathic pain in rat model of spinal cord injury.

INTRODUCTION: Due to side effects of medications used for chronic pain, combination therapy seems to be an appropriate solution for alleviation of chronic pain and reducing the side effects. The role of inhibitory GABA system is well proven in reducing neuropathic pain. Also, special attention has been focused on endogenous morphine (endomorphins) in reducing chronic pain originates from damage to the nervous system. The purpose of this study is to investigate the analgesic effect of simultaneous administration of GABA agonist and endomorphin-1 on neuropathic pain in rat model of spinal cord injury (SCI). The role of oxidative stress, NR1 subunits of NMDA receptors, and α2 subunits of GABA receptors in the spinal cord has also been investigated. METHODS: Spinal cord at level of T6-T8 was compressed. Three weeks after spinal cord injury, muscimol and endomorphin-1 were injected (intrathecally once a day for 7 days) individually or in combination. Mechanical and cold allodynia, thermal and mechanical hyperalgesia were evaluated before injection and 15 and 60 min after injection. At the end of behavioral experiments, histological and biochemical evaluations were done on prepared spinal cord samples. RESULTS: Isobologram results showed that combination therapy significantly increased the pain threshold comparing to injection of endomorphin-1 (EM) or muscimol alone. Histological studies indicated the increased expression of α2 subunits of GABA receptors, and NR1 subunits of NMDA receptors in the spinal cord. The combination therapy also increased the glutathione (GSH) and superoxide dismutase (SOD) level and decreased the malondialdehyde (MDA) levels in the spinal cord. CONCLUSION: Simultaneous administration of muscimol and endomorphine-1 could be a new candidate for alleviation of pain resulting from spinal cord injury.

Assessment of the protective effect of KN-93 drug in systemic epilepsy disorders induced by pilocarpine in male rat.

BACKGROUND AND AIMS: Epileptic seizures occur as a consequence of a sudden imbalance between the stimuli and inhibitors within the network of cortical neurons in favor of the stimulus. One of the drugs that induce epilepsy is pilocarpine. Systemic injection of pilocarpine affects on muscarinic receptors. Increasing evidence has addressed the implication of KN-93 by blocking Ca2+ /calmodulin-dependent protein kinase II (CaMKII), suppressing oxidative stress and inflammation, and also reducing neuron decay. So, we aimed to evaluate the potential preventive effects of KN-93 in systemic epilepsy disorders induced by pilocarpine. MATERIALS AND METHODS: In this animal study, male rats were divided into five groups including treatment group (KN-93 with the dose of 5 mM/10 µL dimethyl sulfoxide (DMSO) before inducing epilepsy by 380 mg/kg pilocarpine) KN-93 group (received 5 mM KN-93), control group, epilepsy group (received 380 mg/kg pilocarpine Intraperitoneal), and sham group (received 10 µL DMSO). Oxidative stress was assessed by measuring its indicators including the concentration of malondialdehyde (MDA), nitrite, glutathione (GSH), as well as the antioxidant activity of catalase. In addition, serum levels of proinflammatory mediators including tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were determined. RESULTS: Pretreatment with KN-93 significantly reduced oxidative stress index by reducing the concentration of MDA, nitrite, and increasing the level of GSH. In addition, low concentrations of TNF-α and IL-1ß were observed in hippocampus supernatant of KN-93 pretreated rats in comparison with the pilocarpine groups. Moreover, administration of KN-93 improved neuronal density and attenuated the seizure activity and behavior. CONCLUSIONS: Overall, our findings suggest that KN-93 can effectively suppress oxidative stress and inflammation. Furthermore, KN-93 is able to attenuate seizure behaviors by preventing its effects on neuron loss, so, it is valuable for the treatment of epileptic seizures.

Huperzine A ameliorates cognitive dysfunction and neuroinflammation in kainic acid-induced epileptic rats by antioxidant activity and NLRP3/caspase-1 pathway inhibition.

Temporal lobe epilepsy (TLE) is one of the most prevalent types of epilepsy in human. Huperzine A (Hup-A) has been reported to possess antioxidative and anti-inflammatory properties; however, its role in TLE induced by kainic acid has not been determined. The current study investigated the protective effects of Hup-A (0.1 mg/kg) in kainic acid-induced model of TLE in the rat. In the current study, it was found that Hup-A significantly prevented the seizure intensity and learning and memory deterioration which was assessed by Morris water maze (MWM) and novel object recognition task (NOR). Additionally, Hup-A inhibited oxidative stress, inflammation, and acetylcholinesterase activity (AChE). In addition, catalase and superoxide dismutase (SOD) activities increased after Hup-A treatment, while malondialdehyde (MDA) and nitrite levels significantly reduced. Regarding inflammation, this drug decreased kainic acid-induced NLRP3 expression in microglial cells and caspase-1 activity in hippocampal tissue, possibly through diminishing oxidative stress. Taken together, our data showed that Hup-A could be a potential protective substance to ameliorate seizure severity and some memory deficits related to epilepsy via attenuating neuroinflammation and protection of neurons.

Key mechanisms underlying netrin-1 prevention of impaired spatial and object memory in Aß1-42 CA1-injected rats.

Alzheimer's disease (AD) is a neurodegenerative disorder with an incompletely defined aetiology that is associated with memory and cognitive impairment. Currently available therapeutics only provide temporary assistance with symptoms. In spite of plentiful research in the field and the generation of thousands of studies, much is still to be clarified on precise mechanisms of pathobiology, prevention modalities, disease course and cure. Netrin-1, a laminin family protein, is said to have anti-inflammatory and anti-apoptotic effects and has a key role in neurogenesis and morphogenesis of neural structures. Accordingly, this study was designed to investigate protective effects of bilateral intrahippocampal fissure microinjections of netrin-1 on memory impairment in rat model of AD. Concomitant administration of netrin-1 with amyloid beta 1-42 (Aß1-42 ) improved cognitive dysfunction in novel object recognition task (NOR), ameliorated impaired spatial memory in Morris water maze (MWM) setting, increased neuronal density and reduced amyloid aggregation in rat AD model. Netrin-1 was also seen to prevent Aß1-42 -induced caspase-3, caspase-7 and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation. Therefore, based on the data reported here, netrin-1 may be a promising biologic therapeutic that addresses the memory and neuronal loss associated with AD.

Stress and sexual reproduction affect the dynamics of the wheat pathogen effector AvrStb6 and strobilurin resistance.

Host resistance and fungicide treatments are cornerstones of plant-disease control. Here, we show that these treatments allow sex and modulate parenthood in the fungal wheat pathogen Zymoseptoria tritici. We demonstrate that the Z. tritici-wheat interaction complies with the gene-for-gene model by identifying the effector AvrStb6, which is recognized by the wheat resistance protein Stb6. Recognition triggers host resistance, thus implying removal of avirulent strains from pathogen populations. However, Z. tritici crosses on wheat show that sex occurs even with an avirulent parent, and avirulence alleles are thereby retained in subsequent populations. Crossing fungicide-sensitive and fungicide-resistant isolates under fungicide pressure results in a rapid increase in resistance-allele frequency. Isolates under selection always act as male donors, and thus disease control modulates parenthood. Modeling these observations for agricultural and natural environments reveals extended durability of host resistance and rapid emergence of fungicide resistance. Therefore, fungal sex has major implications for disease control.

An Audit of Perioperative Antimicrobial Prophylaxis: Compliance with the International Guidelines.

OBJECTIVE: Antimicrobial prophylaxis has been demonstrated to lower the incidence of postoperative infection in nearly all types of surgery. The American Society of Health-System Pharmacists (ASHP) guideline summarizes current data on the appropriate use of antibiotic for surgical prophylaxis. The objective of this study was to assess and audit the use of antibiotics in a tertiary care center according to the recommendation of ASHP guideline. METHODS: This cross-sectional study was performed using prospective data gathered from April to September 2015 in the surgical wards of Al Zahra Hospital, Isfahan, Iran. Antibiotic indication and choice, dose, dosing interval, route of administration, and timing of first administration and duration of prophylaxis were compared with the ASHP guideline recommendations. FINDINGS: A total of 100 patients with the mean age of 49.8 ± 18.2 years were recruited for this study. About 22% of procedures had full compliance with all guideline recommendations. The most frequently encounter noncompliance type were the duration of prophylaxis (14%) and appropriate agent choice (35%). Timing of the initial dose was appropriate in most of the procedures (42%). CONCLUSION: This study revealed that most of the prescribed antibiotics for surgical prophylaxis are not in accordance with standard treatment guideline. The density of antimicrobial use for preoperative antimicrobial prophylaxis is very high. Furthermore, the hospital should develop a formal strategy, including a local guideline for antimicrobial prophylaxis in surgical procedures.

Apolipoprotein A2 -265 T>C polymorphism interacts with dietary fatty acids intake to modulate inflammation in type 2 diabetes mellitus patients.

OBJECTIVE: Several investigations have been conducted regarding the interaction between Apolipoprotein A2 (APOA2) -265 T>C polymorphism and dietary intake of saturated fatty acids (SFAs) on obesity in healthy individuals or type 2 diabetes mellitus (T2 DM) patients. The aim of the present study is to examine the effect of this interaction on inflammatory markers in T2 DM patients. METHODS: This is a comparative cross-sectional study on 180 T2 DM patients with known APOA2 genotype. Dietary intake was assessed by food-frequency questionnaire and serum levels of inflammatory markers (interleukin [IL]-18, pentraxin 3, and high-sensitivity C-reactive protein [hs-CRP]) were measured. The subjects were dichotomized into "high" and "low" categories, based on the median dietary intake of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and SFAs. The data were analyzed by analysis of covariance multivariate interaction model. RESULTS: In CC genotype, higher median intake of ω-3 PUFAs and MUFAs was associated with decreased serum levels of IL-18 and hs-CRP (P = 0.014 and 0.008, respectively). In T-allele carriers, higher median intake of SFAs was associated with increased serum hs-CRP level (P < 0.001). There was a significant relationship between APOA2 polymorphism and ω-3 PUFA intake on serum IL-18 level (P interaction = 0.03). Moreover, the relationship between this polymorphism and SFA and MUFA intake on serum hs-CRP level was statistically significant (P interaction = 0.03 and 0.024, respectively). CONCLUSIONS: In T2 DM patients, the dietary intake of antiinflammatory fatty acids, such as ω-3 PUFAs and MUFAs, could reduce the inflammatory effects associated with the CC genotype. In addition, proinflammatory fatty acids, such as SFAs, could overcome the antiinflammatory effect of the T-allele. Further studies are needed to confirm these findings.

The interaction between ApoA2 -265T>C polymorphism and dietary fatty acids intake on oxidative stress in patients with type 2 diabetes mellitus.

INTRODUCTION: Apolipoprotein A2 (APOA2) -265T>C polymorphism has been studied in relation to oxidative stress and various dietary fatty acids. Since the interaction between APOA2 polymorphism and dietary fatty acids on oxidative stress has not yet discussed, we aimed to investigate the interaction on oxidative stress in type 2 diabetes mellitus (T2DM) patients. METHODS: The subjects were 180 T2DM patients with known APOA2 genotype, either TT, TC or CC. Superoxide dismutase (SOD) activity was determined by colorimetric method. Total antioxidant capacity (TAC) and serum level of 8-isoprostane F2α were measured by spectrophotometry and ELISA, respectively. Dietary intake was collected through a food frequency questionnaire. Based on the median intake, fatty acids intake was dichotomized into high or low groups. The interaction between APOA2 polymorphism and dietary fatty acids intake was analyzed by ANCOVA multivariate interaction model. RESULTS: Higher than median intake of omega-6 polyunsaturated fatty acids (n-6 PUFA) was associated with increased serum level of 8-isoprostane F2α in subjects with TT/TC genotype (p = 0.004), and higher than median intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) was associated with increased serum SOD activity in CC genotype (p < 0.001). There was a statistically significant interaction between APOA2 polymorphism and n-6 PUFA intake on 8-isoprostane F2α concentration as well as n-3 PUFA intake on serum SOD activity (p-interaction = 0.04 and 0.02, respectively). CONCLUSIONS: The current study shows the interaction between APOA2 polymorphism and dietary fatty acids intake on oxidative stress. More investigations on different populations are required to confirm the interaction.