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Nociception is the neuronal process of encoding noxious stimuli and could be modulated at peripheral, spinal, brainstem, and cortical levels. At cortical levels, several areas including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), ventrolateral orbital cortex (VLO), insular cortex (IC), motor cortex (MC), and somatosensory cortices are involved in nociception modulation through two main mechanisms: (i) a descending modulatory effect at spinal level by direct corticospinal projections or mostly by activation of brainstem structures (i.e. periaqueductal grey matter (PAG), locus coeruleus (LC), the nucleus of raphe (RM) and rostroventral medulla (RVM)); and by (ii) cortico-cortical or cortico-subcortical interactions. This review summarizes evidence related to the participation of the aforementioned cortical areas in nociception modulation and different neurotransmitters or neuromodulators that have been studied in each area. Besides, we point out the importance of considering intracortical neuronal populations and receptors expression, as well as, nociception-induced cortical changes, both functional and connectional, to better understand this modulatory effect. Finally, we discuss the possible mechanisms that could potentiate the use of cortical stimulation as a promising procedure in pain alleviation.

Improved estimates of the Malaysian Shadow Economy (SE), illegal money and corrections to the magnitude of SE using the ARDL technique based on the modified Currency Demand Function Model (CDFM) from 1972 to 2012 are provided in this paper. This study rectifies the failure in previous studies to capture the positive and symmetric relationships between the demand for money and per capita income. The use of the scale of real GDP in the Modified CDFM is necessary methodologically to obtain an accurate estimation of SE. This study combines the demand rate of deposits with circulated money as dependent variable, which is more liquid and thus may end up in SE. It considers inequality of the velocity of money in both economies (SE and the formal economy). The variables of opportunity cost of using money in their ratio level rather than logarithm form are used in the modified CDFM. The size of the SE in Malaysia has been fluctuating and averaged around 42.53% of GDP.

Levetiracetam (LEV) has been used for the treatment of epilepsy, especially partial seizures, owing to its pharmacokinetic profile, but the LEV impurity C (IMP C), pyridine-2-ol, is regarded as a main toxic substance. The existing methods for the analysis of LEV and its impurity are not fully effective. This study aimed to develop a simple gas chromatography-mass spectrometric (GC–MS) technique, for the first time, to analyze LEV and its toxic IMP-C without derivatization process, and to compare the technique with the previously reported UPLC method. Two different dosage forms of LEV, i.e. the tablet and syrup, plus IMP-C were determined by the same procedure. The analysis, without any derivatization processes, was performed using the gas chromatography coupled with Single Quadrupole Mass Spectrometer in the selected ion monitoring (SIM) mode that used electron ionization with 70 eV energy from 4 to 400 Amu. The helium carrier gas was run through a TG-5MS column with the flow rate of 1 mL/min via temperature programming. USP validation parameters were employed for the method validation regarding linearity and accuracy. The proposed method was successfully utilized to determine LEV in the tablet and syrup dosage forms. The statistical analysis showed no significant difference (p > 0.05) between this novel technique and the available UPLC method. Overall, the newly developed chromatographic method is characterized as simple and very sensitive for the simultaneous analysis of LEV and its impurity.

Purpose Fine needle aspiration (FNA) is the gold standard for assessment of thyroid nodules, with the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) used to predict the malignancy risk of these nodules. Our aim was to evaluate the diagnostic utility of the TBSRTC for a Saudi population, by comparing the malignancy risk based on histopathology to FNA-based diagnosis of each of the TBSRTC categories and to previously published malignancy risk in other population. Materials and methods This was a retrospective study of the data of 241 patients who underwent FNA assessment of thyroid nodules and surgical resection with histopathology at John Hopkins Aramco Healthcare, Dhahran, Saudi Arabia, between January 2016 and December 2019. Results The malignancy risk for each of the TBSRTC categories was as follows: non-diagnostic, 25%, benign; 5.74%; atypia of undetermined significance, 37%; suspicious for follicular neoplasm, 38%; suspicious for malignancy, 100%; and malignant, 95%. Our finding were comparable to previously published malignancy risks, except for a higher rate of malignancy in the benign category at 18% compared to 0–3%. Conclusion Our findings validate the diagnostic reproducibility of the TBSRTC for a Saudi population, with the risk of malignancy confirmed by histopathological assessment being consistent with those previously reported for other populations.

The aim of the presented work is to compare two popular chemometric methods which are partial least squares regression (PLSR) and support vector regression (SVR). The comparison shows their characteristics via application of the suggested methods to analysis of Norfloxacin (NF) and Tinidazole (TZ) with the presence of a potential impurity of Tinidazole; 2-Methyl-5-nitro-1H-imidazole (MNZ). For appropriate analysis, a 3 factor 4 level experimental design was constructed, which results in a training set composed of 16 mixtures which contains different concentrations of the three components; achieving symmetry, rotatability and orthogonality in mixture space. In order to validate the prediction ability of the suggested models, an independent test set consisting of 8 in-space and 8 out-of-space mixtures was used. The presented results show high specificity and accuracy of the mentioned multivariate calibration models for analysis of in-space samples of NF and TZ in presence of (MNZ) using UV spectral data. Statistical comparisons of predictive abilities of proposed models against classical least squares CLS model and against each other was performed; whether for analysis of test set mixtures or dosage form. CLS model showed lower predictive ability compared to other models. Results obtained by SVR model are as accurate as PLSR model, however, optimization and implementation of PLSR is faster and easier, hence PLSR could be of choice for this given case study. The developed chemometric models were validated as directed by ICH strategies. The validated methods were efficiently used for estimation of NF and TZ in pure powders and pharmaceuticals which indicates their suitability for application in quality control examination of both of the drugs.

A green high performance liquid chromatographic method with ultra violet detector (HPLC-UV) is presented, for the first time, for the simultaneous estimation of two hepatoprotective drugs in capsules and spiked human plasma. The first component is a herbal supplement, namely silymarin (SR) and the second is vitamin E acetate (VE). The method utilized an isocratic elution using C8 column, a mobile phase consisting of methanol:acetonitrile:triethylamine:trifluoroacetic acid (85:15:0.2:0.1, by volume) at 1 mL/min flow rate and 210 nm as a measuring wavelength. All silymarin flavonolignans were measured together as a single peak. The method was evaluated for precision, selectivity, linearity, accuracy, LOQ, and LOD. SR and VE were detected in the linear range of 0.3–50 μg/mL and 0.1 to 50 μg/mL respectively. The Eco-scale score of the new HPLC method was 62 while it was 55 for the previous electrochemical method. Calibration curves had correlation coefficients of >0.999. The new method is better than the old electrochemical voltammetric method in terms of simplicity, greenness, wide linear range and analysis time.

Background : A simple noninvasive test that accurately distinguishes NASH from NAFL as well as determines the disease severity is urgently needed. Recently, it was found that determination of cytokeratin-18 (CK-18) fragments in the blood, predicts and correlates with histological NASH in which there is development of lobular inflammation, cell ballooning and fibrosis, supporting its usefulness in clinical practice. Aims : To evaluate the role of CK-18 as a non invasive marker in diagnosis of NASH and its usefulness in correlation with disease severity in Egyptian patients. Patients and methods : 90 subjects were divided into 3 groups: group I: including 30 patients with NASH, group II: including 30 patients with NAFL, and group III: including 30 healthy subjects as control. Diagnosis of NASH and its discrimination from NAFL was done by liver biopsy. CK-18 level in plasma was measured for all subjects using ELISA. Results : CK-18 was significantly elevated in patients of group I in comparison to group II and III patients, with mean ± SD: 460 ± 279, 167± 56 and 149± 57, respectively, andP value: 0.001. The (ROC) curve diagnostic performance of CK18 in diagnosis of NASH shows: cutoff value of >240 U/L, with sensitivity 76.7%, specificity 95.0%. Ck-18 was found to correlate with disease severity assessed by NAS scoring system with P value: 0.001. Conclusion : Measurement of CK18 in NASH is a useful screening, diagnostic and staging biomarker. Keywords : Cytokeratin 18; NASH; NAFLD; NAFLD activity score; Liver biopsy; Keratins

RP-HPLC chromatographic method was developed for the determination of hyoscine N-butyl bromide (HBB) and Paracetamol (PAR). In this chromatographic method, HBB and PAR were separated using C18 (25 cm × 4.6 mm i.d. 5 μm particle size) column as a stationary phase and water: methanol (50:50, V/V pH adjusted to 3.9 with CF 3 COOH acid) as a mobile phase, maintaining the flow rate at 1.0 mL min −1 with UV detection at 210 nm. The proposed method was successfully applied for the determination of HBB and PAR in pure form over a concentration range of 2.0–50.0 μg mL −1 for HBB with mean percentage recovery of 100.10 ± 0.475 and over a concentration range of 5.0–200.0 μg mL −1 for PAR with mean percentage recovery of 99.87 ± 0.942 and in their pharmaceutical formulations (Buscopan plus® tablets, Buscamol® tablets and Buscopan plus® suppositories).