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The mechanisms of cognitive decline after intraventricular hemorrhage (IVH) in some patients continue to be poorly understood. Multiple rodent models of intraventricular or subarachnoid hemorrhage have only shown mild or even no cognitive impairment on subsequent behavioral testing. In this study, we show that intraventricular hemorrhage only leads to a significant spatial memory deficit in the Morris water maze if it occurs in the setting of an elevated intracranial pressure (ICP). Histopathological analysis of these IVH + ICP animals did not show evidence of neuronal degeneration in the hippocampal formation after 2 weeks but instead showed significant microglial activation measured by lacunarity and fractal dimensions. RNA sequencing of the hippocampus showed distinct enrichment of genes in the IVH + ICP group but not in IVH alone having activated microglial signaling pathways. The most significantly activated signaling pathway was the classical complement pathway, which is used by microglia to remove synapses, followed by activation of the Fc receptor and DAP12 pathways. Thus, our study lays the groundwork for identifying signaling pathways that could be targeted to ameliorate behavioral deficits after IVH.

Our previous studies demonstrated that traumatic brain injury (TBI) and ventricular administration of thrombin caused hippocampal neuron loss and cognitive dysfunction via activation of Src family kinases (SFKs). Based on SFK localization in brain, we hypothesized SFK subtypes Fyn and c-Src, as well as SFK downstream molecule Rho-associated protein kinase (ROCK), contribute to cell death and cognitive dysfunction after TBI. We administered nanoparticle wrapped small interfering RNA (siRNA)-Fyn and siRNA-c-Src, or ROCK inhibitor Y-27632 to adult rats subjected to moderate lateral fluid percussion (LFP)-induced TBI. Spatial memory function was assessed from 12 to 16 days, and NeuN stained hippocampal neurons were assessed 16 days after TBI. The combination of siRNA-Fyn and siRNA-c-Src, but neither alone, prevented hippocampal neuron loss and spatial memory deficits after TBI. The ROCK inhibitor Y-27632 also prevented hippocampal neuronal loss and spatial memory deficits after TBI. The data suggest that the combined actions of three kinases (Fyn, c-Src, ROCK) mediate hippocampal neuronal cell death and spatial memory deficits produced by LFP-TBI, and that inhibiting this pathway prevents the TBI-induced cell death and memory deficits.

Characterization of electrophysiological recordings during deep brain stimulation (DBS) surgery is critical for anatomical targeting and is extensively utilized to investigate physiologic markers of Parkinson’s Disease (PD). Transient improvement in clinical symptoms has been reported after microelectrode penetration, but the mechanism(s) underlying this improvement are not well understood. Thus, we sought to determine the electrophysiologic effects of microelectrode penetration in the Subthalamic Nucleus (STN).

Over one-third of patients with temporal lobe epilepsy are refractory to medication. In addition, anti-epileptic drugs often exacerbate cognitive comorbidities. Neuromodulation is an FDA treatment for refractory epilepsy, but patients often wait >20 years for a surgical referral for resection or neuromodulation. Using a rodent model, we test the hypothesis that 2 weeks of theta stimulation of the medial septum acutely following exposure to pilocarpine will alter the course of epileptogenesis resulting in persistent behavioral improvements. Electrodes were implanted in the medial septum, dorsal and ventral hippocampus, and the pre-frontal cortex of pilocarpine-treated rats. Rats received 30 min/day of 7.7 Hz or theta burst frequency on days 4-16 post-pilocarpine, prior to the development of spontaneous seizures. Seizure threshold, spikes, and oscillatory activity, as well as spatial and object-based learning, were assessed in the weeks following stimulation. Non-stimulated pilocarpine animals exhibited significantly decreased seizure threshold, increased spikes, and cognitive impairments as compared to vehicle controls. Furthermore, decreased ventral hippocampal power (6-10 Hz) correlated with both the development of spikes and impaired cognition. Measures of spikes, seizure threshold, and cognitive performance in both acute 7.7 Hz and theta burst stimulated animals were statistically similar to vehicle controls when tested during the chronic phase of epilepsy, weeks after stimulation was terminated. These data indicate that modulation of the septohippocampal circuit early after pilocarpine treatment alters the progression of epileptic activity, resulting in elevated seizure thresholds, fewer spikes, and improved cognitive outcome. Results from this study support that septal theta stimulation has the potential to serve in combination or as an alternative to high frequency thalamic stimulation in refractory cases and that further research into early intervention is critical.

Carriers of the fragile X premutation (PM) can develop a variety of early neurological symptoms, including depression, anxiety and cognitive impairment as well as being at risk for developing the late-onset fragile X-associated tremor/ataxia syndrome (FXTAS). The absence of effective treatments for FXTAS underscores the importance of developing efficacious therapies to reduce the neurological symptoms in elderly PM carriers and FXTAS patients. A recent preliminary study reported that weekly infusions of Allopregnanolone (Allop) may improve deficits in executive function, learning and memory in FXTAS patients. Based on this study we examined whether Allop would improve neurological function in the aged CGG knock-in (CGG KI) dutch mouse, B6.129P2(Cg)-Fmr1tm2Cgr/Cgr, that models much of the symptomatology in PM carriers and FXTAS patients. Wild type and CGG KI mice received 10 weekly injections of Allop (10 mg/kg, s.c.), followed by a battery of behavioral tests of motor function, anxiety, and repetitive behavior, and 5-bromo-2'-deoxyuridine (BrdU) labeling to examine adult neurogenesis. The results provided evidence that Allop in CGG KI mice normalized motor performance and reduced thigmotaxis in the open field, normalized repetitive digging behavior in the marble burying test, but did not appear to increase adult neurogenesis in the hippocampus. Considered together, these results support further examination of Allop as a therapeutic strategy in patients with FXTAS.

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.

Whether from a fall, sports concussion, or even combat injury, there is a critical need to identify when an individual is able to return to play or work following traumatic brain injury (TBI). Electroencephalogram (EEG) and local field potentials (LFP) represent potential tools to monitor circuit-level abnormalities related to learning and memory: specifically, theta oscillations can be readily observed and play a critical role in cognition. Following moderate traumatic brain injury in the rat, lasting changes in theta oscillations coincide with deficits in spatial learning. We hypothesized, therefore, that theta oscillations can be used as an objective biomarker of recovery, with a return of oscillatory activity corresponding with improved spatial learning. In the current study, LFP were recorded from dorsal hippocampus and anterior cingulate in awake, behaving adult Sprague Dawley rats in both a novel environment on post-injury days 3 and 7, and Barnes maze spatial navigation on post-injury days 8-11. Theta oscillations, as measured by power, theta-delta ratio, peak theta frequency, and phase coherence, were significantly altered on day 3, but had largely recovered by day 7 post-injury. Injured rats had a mild behavioral phenotype and were not different from shams on the Barnes maze, as measured by escape latency. Injured rats did use suboptimal search strategies. Combined with our previous findings that demonstrated a correlation between persistent alterations in theta oscillations and spatial learning deficits, these new data suggest that neural oscillations, and particularly theta oscillations, have potential as a biomarker to monitor recovery of brain function following TBI. Specifically, we now demonstrate that oscillations are depressed following injury, but as oscillations recover, so does behavior.

Focal epilepsies represent approximately half of all diagnoses, and more than one-third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)-approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low-frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA-approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy.

Today, the role of creativity in the world economy and the development process of countries has been assessed as so important and key that creativity has played a significant role in the economic growth and development of the world. On the other hand, the capability of human resources has been able to establish the sustainability of this creativity for different levels of a country. Therefore, the purpose of this research is to analyze the influence of capable households on the formation of creative villages. The purpose of the research is applied, and the research method is descriptive-analytical. Data and information were collected in both documentary and field form (questionnaire) in 5 dimensions of village households' capabilities (effectiveness, meaningfulness, competence, trust and right to choose). The statistical population of the research included heads of households in the villages of Roshtkhar Township, which was calculated based on Cochran's formula, and the sample size of 377 households was calculated and distributed randomly. To analyze the data of the methods, the network analysis model (ANP) and statistical analysis, spatial analysis and Super Decisions, GIS, SPSS software have been used. The realization findings show that the indicators of creativity of households (0.9725), job importance (0.9177), personality of households (0.8847) have the highest weight. Therefore, the fitted model is suitable for conducting the research, which shows a linear and direct relationship between the development of the formation of creative villages and capable rural households in the study area. Rural areas in the villages of Roshtkhar Township can be mentioned to provide financial needs from the managers of relevant government and private institutions. In this regard, considering the trend of globalization of villages, it is suggested that the low level of education among households can be a red light for rural planners. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) can result in persistent cognitive, behavioral and emotional deficits. However, the vast majority of patients are not chronically hospitalized; rather they have to manage their disabilities once they are discharged to home. Promoting recovery to pre-injury level is important from a patient care as well as a societal perspective. Electrical neuromodulation is one approach that has shown promise in alleviating symptoms associated with neurological disorders such as in Parkinson's disease (PD) and epilepsy. Consistent with this perspective, both animal and clinical studies have revealed that TBI alters physiological oscillatory rhythms. More recently several studies demonstrated that low frequency stimulation improves cognitive outcome in models of TBI. Specifically, stimulation of the septohippocampal circuit in the theta frequency entrained oscillations and improved spatial learning following TBI. In order to evaluate the potential of electrical deep brain stimulation for clinical translation we review the basic neurophysiology of oscillations, their role in cognition and how they are changed post-TBI. Furthermore, we highlight several factors for future pre-clinical and clinical studies to consider, with the hope that it will promote a hypothesis driven approach to subsequent experimental designs and ultimately successful translation to improve outcome in patients with TBI.

Traumatic brain injury (TBI) often results in persistent attention and memory deficits that are associated with hippocampal dysfunction. Although deep brain stimulation (DBS) is used to treat neurological disorders related to motor dysfunction, the effectiveness of stimulation to treat cognition remains largely unknown. In this study, adult male Harlan Sprague-Dawley rats underwent a lateral fluid percussion or sham injury followed by implantation of bipolar electrodes in the medial septal nucleus (MSN) and ipsilateral hippocampus. In the first week after injury, there was a significant decrease in hippocampal theta oscillations that correlated with decreased object exploration and impaired performance in the Barnes maze spatial learning task. Continuous 7.7 Hz theta stimulation of the medial septum significantly increased hippocampal theta oscillations, restored normal object exploration, and improved spatial learning in injured animals. There were no benefits with 100 Hz gamma stimulation, and stimulation of sham animals at either frequency did not enhance performance. We conclude, therefore, that there was a theta frequency-specific benefit of DBS that restored cognitive function in brain-injured rats. These data suggest that septal theta stimulation may be an effective and novel neuromodulatory therapy for treatment of persistent cognitive deficits following TBI.

Villages are always a place for invention, innovation, and creativity. With the introduction of creative settlements in rural areas, it is possible to institutionalize decentralization, human resource creativity, public participation, and sustainable rural development in the heart of rural society. Good rural governance is a prerequisite for achieving the above-mentioned things. Therefore, the present research was conducted to analyze the role of management based on good rural governance in the development of creative settlements in rural areas, and villages of Roshtkhar Township. This research is practical in terms of purpose and the research method is descriptive-analytical. Data collection has been done in both documentary and field forms (questionnaire) in the two sectors of good rural governance and the formation of creative settlements. The statistical population of the research included heads of households in the villages of Roshtkhar Township, and based on the Cochran formula, the sample size of 377 households was calculated and distributed randomly. AHP technique, SAR analytical model, Vicor model, and Pearson test were used for data analysis. The research results confirm that good rural governance has changed the quality of life of rural households by creating creative villages and bringing quality to the optimal level for households living in rural areas. The findings of the research indicate that, in 69.9% of the 377 households surveyed, the level of good rural governance has increased in 19.5% of the surveyed households due to creative settlements compared to the last 10 years. The class of good rural governance has decreased due to creative settlements in this time frame. [ABSTRACT FROM AUTHOR]

Purpose- Supporting and stimulating agricultural development has a decisive role in rural development and is considered the main basis of rural development. Therefore, the agricultural sector and rural areas in Iran are still far from the real potentials for development. Therefore, this study aimed at the consequences of creative agriculture and its role in the development of rural areas of Roshtkhar County in Razavi Khorasan province. Design/methodology/approach-This research was an applied one, conducted with descriptive-correlation and causal-relational methods. The statistical population of the research consists of all heads of rural households (21,785) in Roshtkhar County, using the Cochran formula, 377 farmers from the heads of households were selected as a sample. The main tools of the research were researcher-made questionnaire, field observations and library studies. Then, the questionnaires were distributed in 20 villages of the study area. SPSS software and structural equation modeling approach were employed to analyze the data. Findings: The results of the fitted model showed that creative agriculture had the greatest effects on economic (0.405) and social (0.370) variables. The results of investigating the status of creative agriculture in the study area showed that more than 60% of rural farmer households stated that creative agriculture has been able to play a significant role in rural development. Limitations/Strategies: The dispersion of the studied villages to fill out the questionnaire depending on the topic at the village level, the lack of awareness of some rural households towards conducting research projects in order to complete the questionnaire, and finally the costs of conducting this research are challenging of this study. Practical solutions: Finally, according to the results, solutions such as the full implementation of modern irrigation systems, changing the cultivation pattern and using up-to-date machinery and tools in the agricultural sector can improve the results and the consequences of creative agriculture and its role in rural development in the villages and the implementation strategies of this solution are considered necessary. Original/value- This study is significant as the recognition of different issues of creative agriculture at the regional level can help to take an important step in order to improve the condition of rural households in different dimensions (economic, social-cultural, institutional-managerial and physical). [ABSTRACT FROM AUTHOR]

In recent years, increasing attention has been given to improving the energy efficiency of buildings in order to reduce their environmental impact and operational costs. As a result, multi-objective optimization methods have become an important tool for optimizing building energy performance. This research reviews building performance analysis approaches in a comparative method and results in a systematic overview of the existing multi-objective optimization methods used in the field of building energy performance. This review covers a wide range of optimization techniques, including genetic algorithms (NSGA-II), evolutionary algorithms, particle swarm intelligence algorithms, and other metaheuristic approaches. Furthermore, the review provides a comprehensive analysis of the strengths and weaknesses of each method in different fields such as daylight, ventilation, and thermal performance analysis. In order to achieve the aims of the research alongside reviewing the Scopus scientific database, various relevant studies were investigated. Eventually, this study provides. Eventually, this review identifies gaps in the literature potential in research directions and proposes multiple ways for future research. [ABSTRACT FROM AUTHOR]

Purpose- Village as a residential system has always suffered a lot of damage due to natural hazards such as drought throughout history, and due to the dependence of the rural economy on the agricultural sector, any threat against this sector leads to the weakening of the economic foundations, the village and eventually the economic stagnation of the country. Therefore, the aim of the current research is to evaluate the drought-resilient measures to reduce the vulnerability of rural households located in Rostaq district in Khalil-Abad City, Khorasan-Razavi Province . Design/methodology/approach- The type of research is applied research, and the data was collected by applying a descriptive-analytical method by using documentary sources and field studies (questionnaire). The statistical population of the research is comprised of the heads of rural households living in the study area. As a result, 337 people were selected using Cochran's method. For ranking and spatial analysis of the village, Copras and Vicor techniques were used, and Shannon technique and SPSS software were used for statistical data analysis . Findings- The results showed that among the weights obtained from the paired comparison of the dimensions raised in resilience measures with drought in reducing the vulnerability of rural households, modern irrigation measures with a score of (0.290) have the highest score in resilience measures. Avaram took over with the drought. Finally, in the study area, Niqab village performed better than other villages in terms of resilience measures in dealing with drought . Research limitations/implications- Not having access to statistical information when referring to Jihad Agriculture and Governorship, as well as filling out the questionnaire depending on the topic at the village level and the costs of conducting this research are among the challenges of the present research . Practical implications- In the end, according to the obtained results, it is considered necessary to provide solutions for the resilience of rural households at the level of the villages of this district and to implement the solutions . Originality / value- The present research is significant due to its expression and recognition of different issues surrounding the resilience of households in the face of drought. An important step can be taken in the direction of reducing the vulnerability of rural households to deal with drought in the coming years. [ABSTRACT FROM AUTHOR]

Block chain technology, known by popular crypto currencies mainly Bitcoin, is widely used in several fields, not only in the financial sector but also in the healthcare industry as well as supply chain management sectors. To produce an efficient block chain, consensus algorithms are an essential part of it. Proof of Work (POW) and Proof of Stake (POS) protocols are widely used in many block chain networks such as Bitcoin, Ethereum, and Litecoin. Block size optimization solves the trade-off between maximum revenue and becomes an alternative payment system. In this research, differential evolution algorithm was used to determine the size of the blocks. The simulation of this research has been done in MATLAB environment. In order to evaluate the proposed method, two scenarios of the number of miners and the type of request have been used. In this research, statistical criteria have been used to evaluate the proposed method. The criteria used in this research include maximum, minimum, average and standard deviation criteria. The results showed that in the scenario of the number of miners, the best answer was obtained in the case where the number of miners was equal to 3. In the request type scenario, the dependency of the requests has been checked. In this case, requests are considered dependent and non-dependent. The results showed that in the non-dependency mode, the request processing time has decreased because in this mode the requests can be executed simultaneously with each other in the dependency mode, the requests have priority over each other. In this case until the desired request is not executed, the next request cannot be executed. [ABSTRACT FROM AUTHOR]

In this study, the electro-Fenton process (with response surface methodology as an experiments design and optimisation technique) was applied to evaluate the effects of five independent variables on the chemical oxygen demand (COD) and colour removal from paper pulp wastewater (PW). The parameters were statistically optimised under response surface methodology. The optimum conditions for 98.2% of COD and 96.8% of colour removal experimentally were at a reaction time of 30 min, current density of 79.9 mA/cm2, pH of 6.9, hydrogen peroxide (H2O2)/PW volume ratio of 1.7 ml/l, hydrogen peroxide (H2O2)/ferrous ions (Fe2+) molar ratio of 1.6, electrode consumption of 0.1 (g/l) and energy consumption of 1.3 (kWh/m3). In the next step, the filtration process was carried out on the treated effluent obtained at the optimal conditions. Then, this was mixed with activated sludge in a ratio of 1 : 10; 99.9% of COD and colour removal was found after 150 and 60 min, respectively. [ABSTRACT FROM AUTHOR]