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The characterization of interfacing elements of in-vehicle and driver’s anthropometric variables of a randomly selected operators with sample size of 161 subjects of commercial buses in the study area were considered in this work. Participatory ergonomic intervention approach was employed in data mining, opinion gathering and subsequent analysis. Related variables between the two systems were compared to establish fitness as well as the level to which human operator were accommodated in the vehicle dimension. A few cases of misfit were recorded based on drivers’ opinion and the measurements taken. Work related musculoskeletal disorder experienced by the users under study were traceable to inappropriate design variable of the in-vehicle elements.    Â

The study analyses the profitability of poultry egg production in Etim Ekpo Local Area of Akwa Ibom State. Primary data were collected from 75 poultry egg producers selected through a multi-stage sampling technique, using a structured questionnaire. Percentage, frequency and budgetary analysis were used to analyze the data. The findings revealed that majority of poultry egg producers were male representing about 71% of the poultry egg producers, and the mean age was 41 years. The study revealed that, the poultry egg producers in the study area had one form of education or the other which significantly contributed to increase in poultry egg production in the study area. About 83% of the poultry egg producers were married, while the average household size was 4 persons per family. Only 27% of the poultry egg producers accepted that, they belong to Cooperative Society and about 69% had an average income that stood at 70,800 per month. With respect to the profitability of poultry egg production, the result indicated that for every 1 invested in the poultry egg production business, there is a return of 2. The result from budgetary analysis revealed that there is a significant relationship between input and output in poultry eggs production business; more so poultry egg production is a profitable investment. The following recommendations were made: reduction in input cost through subsidy on poultry equipment and credit facilities, and better management practices and encouragement of farm records keeping for profit evaluation. [ABSTRACT FROM AUTHOR]

Extra-adrenal Paragangliomas (EAP) are a subset of neuroendocrine tumours. They may arise in a variety of locations in the body. Paragangliomas in the cauda equina region are uncommon, more so is their occurrence during pregnancy. We present a cauda equina paraganglioma arising in a young pregnant female who presented with back pain, constipation and paraparesis. The MRI showed a lumbosacral intradural extramedullary mass. She underwent surgery - a laminectomy, and the mass was removed. Histology with Immunohistochemistry confirmed the diagnosis of Paraganglioma. This article highlights multidisciplinary management of low back pain coexisting with neurological deficits in pregnancy. It is emphasized that early diagnosis and appropriate management significantly reduce maternal and fetal mortality [ABSTRACT FROM AUTHOR]

The analytical solution to the Schrödinger equation in D-dimensions with multiparameter-type potential were obtained using Nikiforov-Uvarov method, and applying the pekeris approximation to the centrifugal term. For convenience,the equation are reduced to the hypergeometricform,where the energy eigen values and corresponding eigenfunction are obtained.The expectation values (r-2), (q+e2αr)-1 and (q+e2αr)-2 are obtained in D-Dimension using Hellmann-Feynman Theorem. [ABSTRACT FROM AUTHOR]

Introduction: Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors in vitro . Materials and Methods: CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results: The (-)-CBC activated CB2 with an EC 50 of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. Discussion: It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.

Medicinal cannabis is being used worldwide and there is increasing use of novel cannabis products in the community. Cannabis contains the major cannabinoids, Δ 9 -tetrahydrocannabinol (Δ 9 -THC) and cannabidiol (CBD), but also an array of minor cannabinoids that have undergone much less pharmacological characterization. Cannabinol (CBN) is a minor cannabinoid used in the community in "isolate' products and is claimed to have pro-sleep effects comparable to conventional sleep medications. However, no study has yet examined whether it impacts sleep architecture using objective sleep measures. The effects of CBN on sleep in rats using polysomnography were therefore examined. CBN increased total sleep time, although there was evidence of biphasic effects with initial sleep suppression before a dramatic increase in sleep. CBN increased both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The magnitude of the effect of CBN on NREM was comparable to the sleep aid zolpidem, although, unlike CBN, zolpidem did not influence REM sleep. Following CBN dosing, 11-hydroxy-CBN, a primary metabolite of CBN surprisingly attained equivalently high brain concentrations to CBN. 11-hydroxy-CBN was active at cannabinoid CB 1 receptors with comparable potency and efficacy to Δ 9 -THC, however, CBN had much lower activity. We then discovered that the metabolite 11-hydroxy-CBN also influenced sleep architecture, albeit with some subtle differences from CBN itself. This study shows CBN affects sleep using objective sleep measures and suggests an active metabolite may contribute to its hypnotic action., Competing Interests: Competing interests: JCA is Deputy Academic Director of the Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded research program at the University of Sydney. He has served as an expert witness in various medicolegal cases involving cannabis and has received consulting fees from the World Health Organization (WHO), Medical Cannabis Industry Australia (MCIA), and Haleon (consumer healthcare subsidiary of Glaxo Smith-Kline). He reports research grants from the Australian National Health and Medical Research Council (NHMRC) and from the Lambert Initiative for Cannabinoid Therapeutics. He is an inventor on patents WO2019227167 and WO2019071302 issued, which relate to cannabinoid therapeutics. ISM is the Academic Director of the Lambert Initiative for Cannabinoid Therapeutics. He has served as an expert witness in various medicolegal cases involving cannabis and has received consulting fees from Medical Cannabis Industry Australia (MCIA), Althea and Janssen. He currently acts as an advisor/consultant to Kinoxis Therapeutics, Psylo, and Emyria. He reports research grants and salary support from the NHMRC and from Lambert Initiative for Cannabinoid Therapeutics. He is an inventor on patents WO2017004674, WO2018107216, WO2020102857 and AU2022240104, licensed to Kinoxis Therapeutics involving the use of novel small molecules (non-cannabinoid) to treat addictions,opioid withdrawal, aggression and social deficits. He is an inventor on issued patents WO2019227167 and WO2019071302, which relate to cannabinoid therapeutics. All other authors have no competing financial or non-financial interests to declare., (© 2024. The Author(s).)

The worldwide legalization of medicinal cannabis has led to an increased use of products made by commercial operators. These products often contain minor cannabinoids such as cannabinol (CBN) which are advertised to improve sleep. Products are also available in which CBN is combined with conventional therapies, with a common product containing both CBN and the widely used sleep-aid melatonin. The combination of CBN and melatonin provides potential for a pharmacokinetic drug-drug interaction (DDI) given that cannabinoids are known to inhibit drug-metabolizing enzymes. Indeed, we recently reported that CBN potently inhibited the CYP1A2-mediated metabolism of caffeine. CYP1A2 is the major hepatic enzyme involved in the metabolism of melatonin; thus, in this study, we aimed to examine whether CBN inhibited CYP1A2-mediated metabolism of melatonin in vitro and in vivo. We found CBN potently inhibited CYP1A2-mediated metabolism of melatonin and increased the apparent oral bioavailability of melatonin in mice with a four-fold increase in the plasma melatonin exposure. Our results provide an additional example of a potential DDI involving melatonin., (© 2024 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.)

Objective: The cannabinoid cannabidiol has established antiseizure effects in drug-resistant epilepsies such as Dravet syndrome and Lennox-Gastaut syndrome. Amorfrutin 2, honokiol, and magnolol are structurally similar to cannabinoids (cannabis-like drugs) but derive from non-cannabis plants. We aimed to study the antiseizure potential of these compounds in various mouse seizure models. In addition, we aimed to characterize their molecular pharmacology at cannabinoid CB 1 and CB 2 receptors and at T-type calcium channels, which are known targets of the cannabinoids., Methods: Brain and plasma pharmacokinetic profiles were determined. Antiseizure activity was assessed against hyperthermia-induced seizures in a Scn1a +/- mouse model of Dravet syndrome. We then elaborated on the most promising compounds in the maximal electroshock (MES) test in mice and the Gabrb3 +/D120N mouse model of Lennox-Gastaut syndrome. Fluorescence-based assays were used to examine modulatory activity at cannabinoid CB 1 and CB 2 receptors and T-type calcium channel subtypes Ca V 3.1, Ca V 3.2, and Ca V 3.3 overexpressed in mammalian cells. Automated patch-clamp electrophysiology was then used to confirm inhibitory activity on Ca V 3.1, Ca V 3.2, and Ca V 3.3 channels., Results: Magnolol and honokiol had high brain-to-plasma ratios (3.55 and 7.56, respectively), unlike amorfrutin 2 (0.06). Amorfrutin 2 and magnolol but not honokiol significantly increased the body temperature threshold at which Scn1a +/- mice had a generalized tonic-clonic seizure. Both amorfrutin 2 and magnolol significantly decreased the proportion of mice exhibiting hindlimb extension in the MES test. Furthermore, magnolol reduced the number and duration of atypical absence seizures in Gabrb3 +/D120N mice. The three compounds inhibited all T-type calcium channel subtypes but were without specific activity at cannabinoid receptors., Significance: We show for the first time that amorfrutin 2 and magnolol display novel antiseizure activity in mouse drug-resistant epilepsy models. Our results justify future drug discovery campaigns around these structural scaffolds that aim to develop novel antiseizure drugs for intractable epilepsies., (© 2024 International League Against Epilepsy.)

Synthetic cannabinoid receptor agonists (SCRAs) comprise the second largest class of new psychoactive substances (NPS), and typically α-amino acid moieties are incorporated as part of their design. Limited investigation has been performed into elucidating structure-activity relationships around commonly used α-amino acid-derived head groups, mainly with valine and tert -leucine-derived compounds previously described. As such, proactive synthesis, characterisation and pharmacological evaluation were performed to explore structure-activity relationships of 15 α-amino acid derivatives, with both the natural isomers and their enantiomers at CB 1 and CB 2 investigated using a fluorescence-based membrane potential assay. This library was based around the detected SCRAs MPP-5F-PICA, MMB-5F-PICA, and MDMB-5F-PICA, with the latter showing significant receptor activation at CB 1 (pEC 50 = 8.34 ± 0.05 M; E max = 108 ± 3%) and CB 2 = 8.13 ± 0.07 M; 50 = 8.13 ± 0.07 M; E max = 99 ± 2%). Most valine and leucine derivatives were potent and efficacious SCRAs, while smaller derivatives generally showed reduced activity at CB 1 and CB 2 , and larger derivatives also showed reduced activity. SAR trends observed were rationalised via in silico induced fit docking. Overall, while natural enantiomers showed equipotent or greater activity than the unnatural isomers in most cases, this was not universal. As such, a number of these compounds should be monitored as emerging NPS, and various substituents described herein., Competing Interests: There are no financial or other relations that could lead to a conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Triple-negative breast cancers (TNBC) have been particularly challenging to manage due to their lack of intrinsic cellular receptors, with the resultant relatively higher morbidity and mortality. Recently, the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD- L1) immune checkpoint pathway has become the focus of immunotherapy, especially for TNBCs. This study aimed to determine the pattern of expression of PD-L1 in TNBC cases in Benin City., Methods: It was a 3-year retrospective study that involved the PD-L1 immunostaining of the TNBC cases that were diagnosed in the Department of Anatomical Pathology, University of Benin Teaching Hospital, Benin City, from January 1, 2017 to December 31, 2019., Result: Ninety-two cases of TNBC were tested for PD-L1 expression. Thirteen (14.1%) of the TNBC cases were PDL1 positive to varying degrees on tumour and immune cells. Diffuse tumoural PD-L1 staining was seen in 4 (30.8%) of the PD-L1 positive cases. PD-L1 expression was significantly associated with increasing age up to the fifth decade (p =0.030). All the PD-L1 positive TNBC were invasive breast carcinoma of no special type and mostly grade 2 tumours; however, there was no significant association between PD-L1 expression and histological subtype or grade., Conclusion: PD-L1 expression was shown to occur at a relatively low rate among TNBC cases in this environment and was significantly associated with increasing age. This study has shown that 14.1% (1 in 7) of our TNBC patients could benefit from immune checkpoint inhibitor therapy., (Copyright © 2023 by West African Journal of Medicine.)

Background: Carbapenem-resistant Pseudomonas aeruginosa strains are on the rise worldwide. This study characterized clinical isolates of P. aeruginosa from three Nigerian hospitals for carbapenem resistance., Methods: Strains isolated from wounds ( n  = 88), urine/catheter tips ( n  = 25), sputum/tracheotomy aspirates ( n  = 5), ear swabs ( n  = 4) and vaginal swabs ( n  = 1) were identified by MALDI-TOF and antibiotic susceptibility testing was performed using the VITEK 2 system. The genomic DNA of each isolate was subject to sequencing using Illumina and Oxford nanopore technology. Bioinformatics analyses were performed to detect antimicrobial resistance genes, clonal affiliations and phylogenetic relations of 123 non-duplicate P. aeruginosa isolates, whereas assembly of the nanopore reads using the plasmIDent pipeline enabled the identification of plasmids., Results: Forty-three percent of the isolates were resistant to all antibiotic categories tested. More than 40% of the isolates were resistant to the carbapenems imipenem and/or meropenem (39% and 44%, respectively). Among the meropenem-resistant isolates, 48 (89%) carried at least one carbapenemase gene. The predominant one was bla NDM - 1 ( n  = 34), which conferred resistance to all five antibiotic categories and highly increased the MICs of both meropenem and imipenem. The other recurrent carbapenemase genes were bla VIM-2 ( n  = 4), and bla VIM-5-like ( n  = 11), which co-existed with bla NDM-1 in two isolates., Conclusions: The study revealed a high rate of carbapenem resistance and conjugative, broad host range plasmids carrying carbapenemase-encoding genes, especially the NDM-1 type, among isolates of P. aeruginosa . This may forebode the emergency of ubiquitous carbapenem resistance urging the implementation of infection control and antimicrobial stewardship strategies in Nigerian hospitals., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Background: T-type Ca 2+ channels (Ca v 3) represent emerging therapeutic targets for a range of neurological disorders, including epilepsy and pain. To aid the development and optimisation of new therapeutics, there is a need to identify novel chemical entities which act at these ion channels. A number of synthetic cannabinoid receptor agonists (SCRAs) have been found to exhibit activity at T-type channels, suggesting that cannabinoids may provide convenient chemical scaffolds on which to design novel Ca v 3 inhibitors. However, activity at cannabinoid type 1 (CB 1 ) receptors can be problematic because of central and peripheral toxicities associated with potent SCRAs. The putative SCRA MEPIRAPIM and its analogues were recently identified as Ca v 3 inhibitors with only minimal activity at CB 1 receptors, opening the possibility that this scaffold may be exploited to develop novel, selective Ca v 3 inhibitors. Here we present the pharmacological characterisation of SB2193 and SB2193F, two novel Ca v 3 inhibitors derived from MEPIRAPIM. Methods: The potency of SB2193 and SB2193F was evaluated in vitro using a fluorometric Ca 2+ flux assay and confirmed using whole-cell patch-clamp electrophysiology. In silico docking to the cryo-EM structure of Ca v 3.1 was also performed to elucidate structural insights into T-type channel inhibition. Next, in vivo pharmacokinetic parameters in mouse brain and plasma were determined using liquid chromatography-mass spectroscopy. Finally, anticonvulsant activity was assayed in established genetic and electrically-induced rodent seizure models. Results: Both MEPIRAPIM derivatives produced potent inhibition of Ca v 3 channels and were brain penetrant, with SB2193 exhibiting a brain/plasma ratio of 2.7. SB2193 was further examined in mouse seizure models where it acutely protected against 6 Hz-induced seizures. However, SB2193 did not reduce spontaneous seizures in the Scn1a +/- mouse model of Dravet syndrome, nor absence seizures in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). Surprisingly, SB2193 appeared to increase the incidence and duration of spike-and-wave discharges in GAERS animals over a 4 h recording period. Conclusion: These results show that MEPIRAPIM analogues provide novel chemical scaffolds to advance Ca v 3 inhibitors against certain seizure types., Competing Interests: JA, RL, and IM have served as expert witnesses in various medicolegal cases involving cannabis and cannabinoids. JA, LA, and IM. hold patents on cannabinoid therapies (PCT/AU2018/05089 and PCT/AU2019/050554). JA has received consulting fees from Creo Inc. and Medicinal Cannabis Industry Australia (MCIA). RL acts as a consultant to Shackleford Pharma Inc. IM acts as a consultant to Kinoxis Therapeutics and has received honoraria from Janssen. He has also received consulting fees from MCIA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Harman, Udoh, McElroy, Anderson, Kevin, Banister, Ametovski, Markham, Bladen, Doohan, Greba, Laprairie, Snutch, McGregor, Howland and Arnold.)

Introduction: Cannabidiol (CBD) has been clinically approved for intractable epilepsies, offering hope that novel anticonvulsants in the phytocannabinoid class might be developed. Looking beyond CBD, we have recently reported that a series of biosynthetic precursor molecules found in cannabis display anticonvulsant properties. However, information on the pharmacological activities of these compounds on CNS drug targets is limited. The current study aimed to fill this knowledge gap by investigating whether anticonvulsant phytocannabinoids affect T-type calcium channels, which are known to modulate neuronal excitability, and may be relevant to the anti-seizure effects of this class of compounds. Materials and methods: A fluorescence-based assay was used to screen the ability of the phytocannabinoids to inhibit human T-type calcium channels overexpressed in HEK-293 cells. A subset of compounds was further examined using patch-clamp electrophysiology. Alphascreen technology was used to characterise selected compounds against G-protein coupled-receptor 55 (GPR55) overexpressed in HEK-293 cells, as GPR55 is another target of the phytocannabinoids. Results: A single 10 µM concentration screen in the fluorescence-based assay showed that phytocannabinoids inhibited T-type channels with substantial effects on Ca v 3.1 and Ca v 3.2 channels compared to the Ca v 3.3 channel. The anticonvulsant phytocannabinoids cannabigerovarinic acid (CBGVA) and cannabidivarinic acid (CBDVA) had the greatest magnitudes of effect (≥80% inhibition against Ca v 3.1 and Ca v 3.2), so were fully characterized in concentration-response studies. CBGVA and CBDVA had IC 50 values of 6 μM and 2 µM on Ca v 3.1 channels; 2 μM and 11 µM on Ca v 3.2 channels, respectively. Biophysical studies at Ca v 3.1 showed that CBGVA caused a hyperpolarisation shift of steady-state inhibition. Both CBGVA and CBDVA had a use-dependent effect and preferentially inhibited Ca v 3.1 current in a slow inactivated state. CBGVA and CBDVA were also shown to antagonise GPR55. Conclusion and implications: These findings show that CBGVA and CBDVA inhibit T-type calcium channels and GPR55. These compounds should be further investigated to develop novel therapeutics for treating diseases associated with dysfunctional T-type channel activity., Competing Interests: JA and IM have served as expert witnesses in various medicolegal cases involving cannabis and cannabinoids. JA, LA, and IM hold patents on cannabinoid therapies (PCT/AU2018/05,089 and PCT/AU2019/050,554). JA has received consulting fees from Creo Inc. And Medicinal Cannabis Industry Australia (MCIA). IM acts as a consultant to Kinoxis Therapeutics and has received honoraria from Janssen. He has also received consulting fees from MCIA. CB is a founder and shareholder of Zymedyne Therapeutics. Zymedyne is not a publicly traded entity. The remaining authors have no conflicts of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Udoh, Bladen, Heblinski, Luo, Janve, Anderson, McGregor and Arnold.)

Background: Neuropathology is fundamental to neurology, neurosurgery, and neuroscience practice in general. In parts of Nigeria and other sub-Saharan African countries, Neuropathology is just emerging, and more so Paediatric Neuropathology. Paediatric Neuropathology encompasses diseases of brain, spinal cord, nerves and muscle, affecting infants, children and adolescents, many of which are surgically managed or biopsied for diagnosis., Aim: To determine the pattern of neurosurgical lesions in children diagnosed in Benin-City, Nigeria., Methods: A retrospective database study of biopsies from paediatric patients with neurosurgical lesions histologically evaluated at the Department of Pathology, University of Benin Teaching Hospital, Benin-City, Nigeria, between January 2007 and December 2020 was done. Demographic and clinical data were extracted from Departmental Records; histopathological diagnoses confirmed; and data analyzed using SPSS 20.0., Results: A total of 178 biopsies reviewed. Ages ranged between 2 days and 16 years. Male: female ratio was 1.02:1. There were 87 spinal; 53 intracranial; 32 skull; and 9 scalp lesions. Commonest were Neural tube defects - 56.7% (mostly myelomeningoceles); Intracranial neoplasms - 20.22% (mostly pilocytic astrocytoma and embryonal tumors); Intracranial suppurative lesions -5.06% and dermoid/epidermoid cysts - 5.06%., Conclusion: Most Paediatric neuropathological conditions encountered in our environment can be managed with good outcomes if correctly and promptly diagnosed. There is a need to channel resources into prevention and prenatal diagnoses of NTDs; early diagnosis and management of brain tumors and other intracranial lesions; and better management of otorhinolaryngologic and intracranial infections in children. Neuropathology training and capacity development is also needed., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2022 by West African Journal of Medicine.)

Objective: Cannabigerolic acid (CBGA), a precursor cannabinoid in Cannabis sativa, has recently been found to have anticonvulsant properties in the Scn1a +/- mouse model of Dravet syndrome. Poor brain penetration and chemical instability of CBGA limits its potential as an anticonvulsant therapy. Here, we examined whether CBGA methyl ester, a more stable analogue of CBGA, might have superior pharmacokinetic and anticonvulsant properties. In addition, we examined whether olivetolic acid, the biosynthetic precursor to CBGA with a truncated (des-geranyl) form, might possess minimum structural requirements for anticonvulsant activity. We also examined whether olivetolic acid and CBGA methyl ester retain activity at the epilepsy-relevant drug targets of CBGA: G-protein-coupled receptor 55 (GPR55) and T-type calcium channels., Methods: The brain and plasma pharmacokinetic profiles of CBGA methyl ester and olivetolic acid were examined following 10 mg/kg intraperitoneal (i.p.) administration in mice (n = 4). The anticonvulsant potential of each was examined in male and female Scn1a +/- mice (n = 17-19) against hyperthermia-induced seizures (10-100 mg/kg, i.p.). CBGA methyl ester and olivetolic acid were also screened in vitro against T-type calcium channels and GPR55 using intracellular calcium and ERK phosphorylation assays, respectively., Results: CBGA methyl ester exhibited relatively limited brain penetration (13%), although somewhat superior to that of 2% for CBGA. No anticonvulsant effects were observed against thermally induced seizures in Scn1a +/- mice. Olivetolic acid also showed poor brain penetration (1%) but had a modest anticonvulsant effect in Scn1a +/- mice increasing the thermally induced seizure temperature threshold by approximately 0.4°C at a dose of 100 mg/kg. Neither CBGA methyl ester nor olivetolic acid displayed pharmacological activity at GPR55 or T-type calcium channels., Conclusions: Olivetolic acid displayed modest anticonvulsant activity against hyperthermia-induced seizures in the Scn1a +/- mouse model of Dravet syndrome despite poor brain penetration. The effect was, however, comparable to the known anticonvulsant cannabinoid cannabidiol in this model. Future studies could explore the anticonvulsant mechanism(s) of action of olivetolic acid and examine whether its anticonvulsant effect extends to other seizure types., (© 2021. The Author(s).)

Background: Intracranial extensions of Head and Neck region tumours are a result of direct spread, into the brain and meninges, of tumours arising in the pharynx, paranasal sinuses, orbit, middle ear, scalp, skull and neck tissues. Presenting features may resemble those of an intracranial mass, or the contiguous structure of origin, or both. Delayed diagnosis is not uncommon when patients are not able to afford diagnostic imaging or when the possibility of an intracranial extension is not readily considered in the evaluation of patients with head and neck lesions., Aim: To highlight the important histologic entities in the head and neck region presenting as intracranial mass lesions., Methods: This was a retrospective database study of tumours in the head and neck region with extension into the cranial cavity., Results: We present 13 patients with intracranial extension of tumours from contiguous structures. There were 7 males and 6 females. Age ranged from 16 to 80 years. Mean age of the patients was 48.92 ± 19.13 years. Specific histologic entities included: nasopharyngeal carcinoma, olfactory neuroblastoma, squamous cell carcinoma, rhabdomyosarcoma and adenoid cystic carcinoma, amongst others CONCLUSION: Early and accurate diagnosis requires a raised awareness of tumours in the head and neck region; their likelihood to invade the cranial cavity; and a familiarity with the likely presentation. Multidisciplinary approach is needed when clinical and radiological features are suggestive of mass lesions breaching the skull and invading the brain from adjacent structures. Confirmation of clinical suspicion by histology is essential.

Chordomas are rare, aggressive, bone cancers with notochordal differentiation, a marked predilection for the axial skeleton, and higher incidence in males. Approximately 30% of chordomas occur at the skull base where they make up 0.1-0.2% of all intracranial neoplasms, and 6-16% of skull base neoplasms. Skull base chordomas typically occur between 20 and 40 years of age. We report a case of skull base chordoma in a 35 year old man, who presented with a 10 year history of symptoms, and died before treatment could be instituted. Late presentation and delay in treatment are contributing factors in the demise of this patient. The need for a high index of suspicion, early imaging and prompt referral in patients with symptoms attributable to an intracranial tumor is emphasized.

Background and Purpose: Cannabichromene (CBC) is one of the most abundant phytocannabinoids in Cannabis spp. It has modest antinociceptive and anti-inflammatory effects and potentiates some effects of Δ 9 -tetrahydrocannabinol in vivo. How CBC exerts these effects is poorly defined and there is little information about its efficacy at cannabinoid receptors. We sought to determine the functional activity of CBC at cannabinoid CB 1 and CB 2 receptors., Experimental Approach: AtT20 cells stably expressing haemagglutinin-tagged human CB 1 and CB 2 receptors were used. Assays of cellular membrane potential and loss of cell surface receptors were performed., Key Results: CBC activated CB 2 but not CB 1 receptors to produce hyperpolarization of AtT20 cells. This activation was inhibited by a CB 2 receptor antagonist AM630, and sensitive to Pertussis toxin. Application of CBC reduced activation of CB 2 , but not CB 1 , receptors by subsequent co-application of CP55,940, an efficacious CB 1 and CB 2 receptor agonist. Continuous CBC application induced loss of cell surface CB 2 receptors and desensitization of the CB 2 receptor-induced hyperpolarization., Conclusions and Implications: CBC is a selective CB 2 receptor agonist displaying higher efficacy than tetrahydrocannabinol in hyperpolarizing AtT20 cells. CBC can also recruit CB 2 receptor regulatory mechanisms. CBC may contribute to the potential therapeutic effectiveness of some cannabis preparations, potentially through CB 2 receptor-mediated modulation of inflammation., (© 2019 The British Pharmacological Society.)

Background: Endoscopic biopsy of the gastric mucosa allows early diagnosis, grading, staging and classification of gastric diseases. Helicobacter pylori, has been recognized as a major aetiologic factor for chronic gastritis, benign gastric ulcers and gastric adenocarcinoma and lymphoma. The loco-regional variability in the prevalence of Helicobacter pylori and associated diseases in Nigeria, emphasise the need for evaluation of subsets of a heterogeneous population like ours., Objective: To determine the frequency of helicobacter pylori in gastric endoscopic biopsies and document the pathology of gastric lesions commonly associated with Helicobacter pylori infection., Design: Retrospective descriptive study., Settings: University of Benin Teaching Hospital (UBTH), and Biogenics Histopathology Laboratory (a private Histopathology Laboratory), both based in Benin City, Niger Delta region of Nigeria., Subjects: Endoscopic gastric biopsies recorded in the surgical pathology register of the department from 2005-2009 were studied and relevant demographic and clinical information extracted from the registers, original request cards and patient case files. The clinical data and slides processed from paraffin embedded tissue blocks of endoscopic biopsies of gastric lesions seen from year 2005 to 2009 were studied, analyzed and statistically presented., Results: Total number of specimens studied was 142. Chronic gastritis was present in 117(82.39%) specimens; 9(6.34%) were benign gastric ulcers; 3(2.11%) were gastric polyps; and 11(7.75%) were gastric malignancies. Helicobacter pylori, was demonstrated in 55.6% of all specimens. The peak age for Chronic Gastritis and Gastric Cancer is the 6th decade. Amongst patients with chronic gastritis, inflammatory activity was present in 65%; atrophy in 53%; and intestinal metaplasia in 16.6%. All gastric malignancies seen were intestinal type adenocarcinomas., Conclusion: The spectrum of lesions diagnosed in gastric endoscopic biopsy specimens in Benin, their frequency and associations are largely comparable to what has been described elsewhere in Nigeria and Africa.

Introduction: Traumatic posterior dislocation of the hip (TPDH) is considered an absolute orthopeadic emergency and the outcome of management and prognosis is time dependent. The optimum time within which reduction should be achieved to yield excellent result has remained an issue of considerable controversy. In this paper we evaluated the influence of interval between injury and reduction of dislocation on the choice and outcome of management of TPDH., Method: This is a five year prospective and multicenter study in North-central Nigeria., Patients and Methods: Patients with TPDH, who were treated and had a minimum follow up of 24 months, were included in this study. Reduction was achieved under general anaesthsia. Outcome of treatment was evaluated using the clinical criteria proposed by Matta., Results: Forty-seven patients were evaluated comprising 36 (76.6%) males and 11 (23.4%) females. The commonest cause of injury was road traffic accident in 40 (85.1%). Presentation was considered as early if patient presented within 6 hours of injury and late if later than this. Using Thompson and Epstein's (TE) classification of posterior dislocation of the and Pipkin's (P) sub-classification of type 5, there were 10TE1; 25TE2; 9TE3; 2TE4 and 1 TE5P2. TE1 and TE2 make up 74.5% of cases. 32 (68.1%) presented early and 15 (31.9%) late. Thirty nine patients had successful closed reduction comprising 32 that presented early and seven late. The mean interval between injury and reduction was 9.7 (+/- 1.2) hours. Two (4.3%) patients were reduced within 6 hours, 32 (68.1%) were reduced within 7-12 hours. Five patients had open reduction and three had salvage Girdlestone pseudo-arthroplasty. Outcome assessment showed in the closed reduction group, 22 (59.5%) had excellent score, and 11 (29.7%) had good. These patients were all reduced within 12 hours. Two each had fair and poor outcome while two were lost to follow up. Seventeen (36.2%) developed complications comprising 12 (70.6%) who presented late and five (29.4%) who came in early. The commonest complication was avascular necrosis of the femoral head in eight (47.1%), all presented late with intractable pain; eight (47.1%) with pain of unknown origin and one (5.8%) with sciatic nerve injury which resolved on conservative management., Conclusion: Reduction of PDH within 12 hours is associated with excellent results and few minor complications.