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Pentylenetetrazole- (PTZ)-induced kindling is a broadly used experimental model to evaluate the impact of antiseizure drugs and their novel combination on seizure progression. The current study aimed to evaluate the anti-kindling effects of ivermectin (IVM) and rufinamide (RUFI) alone and their combination with vitamin E. The mice were administered 11 injections of PTZ (40 mg/kg) followed by assessment for anxiety-like behavior and cognitive abilities in a series of behavior tests with subsequent brain isolation for biochemical and histopathological evaluation. The outcomes showed a marked protection by IVM + RUFI (P<0.001) from kindling progression, anxiety-like behavior and cognitive deficit. However, additional supplementation with vitamin E worked superior to duo therapy as these mice were noted to be most fearless to visiting open, illuminated and elevated zones of open field, light/dark and elevated-plus maze (P<0.0001). Further, they showed marked remembrance of the familiar milieu in y-maze (P<0.01) and novel objection recognition (P<0.05) tests. Additionally, their recollection of aversive stimuli in passive avoidance and spatial memory in Morris water maze were evident (P<0.0001), in comparison to kindled mice. The IVM + RUFI duo therapy and its co-administration with vitamin E prevented kindling-triggered oxidative stress in brains and neuronal damage in hippocampus. We conclude that the benefits of the co-administration of vitamin E might be the results of antioxidant and anti-inflammatory effects of vitamin E which might be potentiating the antiseizure effects of RUFI and GABA-A modulating potential by ivermectin. [ABSTRACT FROM AUTHOR]

The anniversary of the publication of 'One Flew Over the Cuckoo's Nest' by Ken Kesey offers an opportunity for reflection on the use of neurosurgery in psychiatry. We used a narrative, historical and dialectical method to deliver an account of the controversial subject. A balanced representation of the negative and positive aspects, acknowledging some of the questionable ethical practices while describing well-reasoned applications is provided. It includes neurosurgeons, psychiatrists who have embraced these procedures with unwarranted enthusiasm and those who have opposed. Neurosurgical techniques for the treatment of severe mental disorders have evolved from rudimentary procedures which were used to 'correct' unwanted behaviours associated with a wide range of severe mental disorders to more refined and selective approaches used as a last resort to treat specific mental health conditions. In the absence of specific aetiological models to guide ablative surgical targets, non-ablative, stimulatory techniques have more recently been developed to allow reversibility when surgical treatment fails to obtain a sizeable improvement in quality of life. The subject is concretely illustrated by two eloquent clinical images: one on a series of brain computed tomography scans carried out on a Canadian population of subjects, who underwent leukotomy decades ago, and the other more contemporary on an implantation surgery to epidural stimulation. Alongside technical advances in psychosurgery, a regulatory framework has gradually developed to ensure vigilance in the appropriateness of patients' selection. Nevertheless, harmonisation of protocols around the world is necessary to ensure consistency in obtaining and maintaining the highest possible ethical standards for the benefit of patients. If the neurosciences promise today, in their new, better framed, and reversible applications, to provide answers to unmet therapeutic needs, we still must remain attentive to drifts linked the introduction of intrusive technologies for purposes of domination or behaviour modification that would impede our individual freedom. [ABSTRACT FROM AUTHOR]

The COVID-19 outbreak has affected numerous facets of human life. It is still an ongoing epidemic with multiple variants emerged since its first outbreak. To detect COVID-19 machine learning and the Internet of Things are the most widely proposed methods in the literature showing favorable performance. This paper presents a complete mapping and assessment of recent research efforts on COVID-19 detection using both machine learning techniques and the Internet of Things devices. The objective of this research work is to identify machine learning techniques and IoT devices that are used in combination to effectively detect COVID-19 and its variants. The synthesis of the mapping study is provided as the analysis of the IoT devices, and the effectiveness of machine learning techniques in disease detection. This study will help the researchers and health practitioners in deploying an effective method for detecting COVID-19, and its variants using machine learning techniques and IoT devices. [ABSTRACT FROM AUTHOR]

Resveratrol is a polyphenolic phytocompound known to possess anxiolytic-like effects but its impact on central gammaaminobutyric acid (GABA) modulation has never been explored. The purpose of this study was to analyze the anxiolytic-like effects of resveratrol alone and in combination with rufinamide, an antiepileptic drug which has never been studied for its anxiolytic potential. The BALB/c mice were tested in a battery of behavior testing after administration of resveratrol (50 mg/kg) and rufinamide (50 mg/kg) alone and in combination. Moreover, molecular docking studies were also carried out to understand the interaction of resveratrol and rufinamide with GABA aminotransferase, GABA receptor and GABA-A transporter type 1. Resveratrol alone exerted notable anxiolytic-like effects and improved outcomes in few experiments but rufinamide alone did not yield any beneficial outcomes. However, the animal co-administered with resveratrol and rufinamide behaved exceptionally well (p<0.05) and preferred open, illuminated and exposed areas of open field, light/dark and elevated plus maze. Further, these animals showed reduced anxiety towards anxiogenic stimuli i.e. holes and marbles in hole board and marble bury tests, respectively. Resveratrol and rufinamide showed moderate to strong binding affinities with GABA proteins, indicating the potential to treat anxiety-like neurological disorders. Moreover, resveratrol and rufinamide were analyzed using molecular docking to determine their interaction with GABA receptors, transporters, and transaminase. The results suggest that their anxiolytic-like effects may be due to inhibiting GABA reuptake transporter 1 protein, leading to increased synaptic levels of GABA neurotransmitter, as seen in stable molecular dynamics results with the 7SK2 GABA transporter protein. [ABSTRACT FROM AUTHOR]

The increasing burden of neurological disorders is becoming a worldwide health challenge and researchers are continuously struggling to cure them by utilizing the miraculous medicinal properties of plants. The crude methanolic extract of whole herb of Phyla nodiflora (Pn.Cr) was subjected to phytochemical, antioxidant and neuropharmacological assessment. The Pn.Cr was initially exposed to the in vitro examination for phytocomposition through ultra-high performance liquid chromatography (UHPLC). The Sprague Dawley rats were chronically administered with various doses (100, 200 and 300 mg/kg) of Pn.Cr for one month with subsequent exposure to neurobehavioral and biochemical experimentation. The Pn.Cr exhibited a dose-dependent anxiolytic effect (P < 0.05 in comparison to control) as rats preferred central, illuminated and open arm zones in open field (OFT), light/dark (L/D) and elevated plus maze (EPM) tests. Likewise, scopolamine-induced amnesia was noticeably reversed with P < 0.05 by Pn.Cr as animals showed improved spontaneous alternation, discrimination index and shorter escape latencies in Y-maze, novel object recognition (NOR) and Morris water maze (MWM) tests. Subsequently, in vivo enzymatic assays depicted the reduced acetylcholinesterase and malondialdehyde levels. The levels of oxidative stress combating enzymes (glutathione peroxidase and superoxide dismutase) were increased in a dose-dependent style. The UHPLC detected 22 phytocompounds were further investigated in silico studied to predict the interaction of blood-brain barrier (BBB) crossing phytocompounds with human acetylcholinesterase. The four BBB crossing phytocompounds belonging to flavonoids, chalcones and alkaloids showed possible interaction with the target enzyme. We found that the phytocompounds owned by Pn.Cr might be playing multiple roles in modulation of different pathways to hinder the pathophysiology of neurological disorders including anxiety and Alzheimer’s disease. [ABSTRACT FROM AUTHOR]

Introduction: Approximately 75% of women aged between 45 years and 55 years suffer from symptoms of menopause. Untreated hot flashes have many downstream effects including but not limited to fatigue, low energy, memory complaints, lowered libido, sexual dysfunction and may even be linked to increased cardiovascular disease. While the gold standard for effective treatment is hormonal therapy, many women (especially those with a family history of breast cancer) may decline their use due to concerns regarding efficacy and safety. Lack of sensitivity training and level of comfort to disclose menopausal symptoms is often a significant barrier to effective treatment. Dose optimization, close surveillance of efficacy of hormone utilization is essential to maintain patient compliance. Objective: Menopausal hot flashes are associated with a variety of downstream sexual complaints including lowered libido. This retrospective study was done to assess if optimal treatment of hot flashes with hormones and over the counter products would have a downstream effect on concurrent reported sexual complaints. Methods: A retrospective review of a random convenience sample was conducted to assess women who presented with complaints of hot flashes. Concurrent associated symptoms were also reported. Treatment interventions and symptom resolution was evaluated. Data was collected and stored in private HIPPA protected database. Results: A random convenience sample (n=56) from the HerMD centers (Cincinnati and Kentucky) was assessed for women (mean age 51.3; range 30-73) who presented with complaints of hot flashes. Associated symptoms included: brain fog/memory complaints (66%); sleep disturbances including insomnia (59%), decreased libido (49%), weight management concerns (38%), vaginal dryness (31%) and dyspareunia (14%). A family history of breast cancer was present in 18% of the sample. Treatment included: behavioral intervention counseling (100%), over the counter supplements n=2, (3.5%) and systemic hormonal therapy n=54 (96.5%) and over the counter recommendations (100%). All patients (100%) with a family history of breast cancer received hormonal therapy. Overall, 96% of patients responded to their intervention with self-reported improvement in hot flashes, and improvement in dyspareunia, vaginal dryness and improved libido at scheduled follow up visits. Patients had multiple office/telehealth visits to ensure dose optimization, efficacy of symptom resolution and ensure no treatment emergent adverse effects. There were n=3 (5%) reported adverse effects (minimal vaginal spotting) yet no patients discontinued treatment Conclusions: Hot flashes are associated with a variety of sexual complaints including but not limited to decreased libido (49%), vaginal dryness (31%) and dyspareunia (14%). Optimal treatment of hot flashes will have downstream efficacy with FSD complaints. At HerMD, HCP have internal continuing menopausal medical education which includes standardized clinical algorithms, bibliotherapy, article data base, 1-1 didactic education/supervision and preceptorships with national menopausal experts. Systemic hormones will help with vaginal dryness and dyspareunia. HerMD advocates close clinical surveillance with treatment efficacy and safety review which allows for interventions to be modified henceforth allow for outcome optimization and enhance compliance. Disclosure: Any of the authors act as a consultant, employee or shareholder of an industry for: Michael Krychman is a consultant for exeltis pharmaceuticals, Astellas, Uberlube and CEEK. [ABSTRACT FROM AUTHOR]

We introduce a novel strategy of fabricating nanoporous carbons loaded with different amounts of CuO nanoparticles via a hard templating approach, using copper-containing mesoporous silica as the template and sucrose as the carbon source. The nature and dispersion of the CuO nanoparticles on the surface of the nanoporous carbons were investigated by x-ray diffraction (XRD), high-resolution scanning electron microscopy (HRSEM) and high-resolution transmission electron microscopy (HRTEM). XRD results reveal that nanoporous carbons with embedded CuO nanoparticles exhibit a well-ordered mesoporous structure, whereas the nitrogen adsorption measurements indicate the presence of excellent textural characteristics such as high surface area, large pore volume and uniform pore size distribution. The amount of CuO nanoparticles in the nanochannels of the nanoporous carbon could be controlled by simply varying the Si/Cu molar ratio of the mesoporous silica template. Morphological characterization by SEM and TEM reveals that high-quality CuO nanoparticles are distributed homogeneously within the nanoporous carbon framework. The supercapacitance behavior of the CuO-loaded nanoporous carbons was investigated. The material with a small amount of CuO in the mesochannels and high surface area affords a maximum specific capacitance of 300 F g-1 at a 20 mV s-1 scan rate in an aqueous electrolyte solution. A supercapacitor containing the CuO-loaded nanoporous carbon is highly stable and exhibits a long cycle life with 91% specific capacitance retained after 1000 cycles.

Rumen Yeast® (RY; Saccharomyces cerevisiae), a live yeast strain, improves milk yield and composition and nutrients digestibility through balancing rumen ecosystem and increasing ruminal cellulolytic bacteria numbers in cattle. To examine the effects of dietary supplementation of RY in Nili-Ravi buffaloes, 16 buffaloes with 8 L average daily milk production were randomly divided into two groups, and investigated for a 60-day period. Group I (control) was offered maize silage ad libitum as sole forage plus 3 kg of concentrate/head per day (16% crude protein (CP) and 72% total digestible nutrients (TDN)), while group II was given the same diet as control supplemented with RY (14 g/head per day). Feed intake, nutrient digestibility, rumen fermentation and milk production of each animal were recorded. Average dry matter (DM) intake was not affected (P>0.05) in buffaloes with or without RY (14.7 and 14.3 kg/day, respectively). Digestibility of DM, CP, and ruminal pH were similar (P>0.05) between the groups, but the digestibility coefficients of neutral detergent fiber and acid detergent fiber were greater (P<0.05) for the animals that received RY. Milk production (9.60 vs. 9.15 L/day) and 4% fat corrected milk (FCM) (11.32 vs. 11.85 L/day) were significantly (P<0.05) greater in the buffaloes fed with RY than the control group. Milk composition was similar between the experimental groups, however, milk somatic cell count (SCC) was significantly (P<0.01) lower in RY supplemented buffaloes than the control animals. In conclusion, feeding RY had positive effects on milk production, fibre digestibility and SCC in buffaloes fed maize silage-concentrate based diet. [ABSTRACT FROM AUTHOR]

The experiment was conducted to investigate the poßibility of replacing cottonseed cake (CSC) with rapeseed cake (RSC) and maize gluten feed 30% (MGF) as protein equivalent basis in Sahiwal calves fed maize silage as basal diet. Twelve male calves (about 12-14 months old, and average body weight 110.5±9 kg) were randomly divided into I, II and III groups with 4 calves in each. Three iso-nutritious (CP 15% and TDN 72%) concentrates with CSC, RSC and MGF silage ad-libitum as basal diet. Results revealed non-significant difference (P>0.05) in total dry matter (DM) intake among the groups, however, daily weight gain (kg/head) by group III (0.78) was 18% and 23% higher (P<0.05) compared to group I (0.66) and II (0.63). Similarly, better feed conversion ratio was observed in group III (5.51) followed by group II (6.46) and I (6.53). The digestibility of DM, neutral detergent fibre and acid detergent fibre was alike among the groups whereas, CP digestibility and N retention was significantly (P<0.05) higher in group III compared to other groups. The economic benefits (ratio of output to input) was higher with MGF (1.29) followed by RSC (1.08) and CSC (1.00). These results suggest that MGF protein source is the best when compared with CSC or RSC on protein equivalent basis in terms of higher growth rate, nutrient digestibility and economic benefits in calves fed maize silage as basal diet. [ABSTRACT FROM AUTHOR]