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The aim of the study was to compare the long-term efficacy of high versus low frequency repetitive transcranial magnetic stimulation (rTMS), applied bilaterally over the dorsolateral prefrontal cortex (DLPFC), on cognitive function and cortical excitability of patients with Alzheimer's disease (AD). Forty-five AD patients were randomly classified into three groups. The first two groups received real rTMS over the DLPFC (20 and 1 Hz, respectively) while the third group received sham stimulation. All patients received one session daily for five consecutive days. In each session, rTMS was applied first over the right DLPFC, immediately followed by rTMS over the left DLPFC. Mini Mental State Examination (MMSE), Instrumental Daily Living Activity (IADL) scale and the Geriatric Depression Scale (GDS) were assessed before, after the last (fifth) session, and then followed up at 1 and 3 months. Neurophysiological evaluations included resting and active motor threshold (rMT and aMT), and the duration of transcallosal inhibition (TI) before and after the end of the treatment sessions. At base line assessment there were no significant differences between groups in any of the rating scales. The high frequency rTMS group improved significantly more than the low frequency and sham groups in all rating scales (MMSE, IADL, and GDS) and at all time points after treatment. Measures of cortical excitability immediately after the last treatment session showed that treatment with 20 Hz rTMS reduced TI duration. These results confirm that five daily sessions of high frequency rTMS over the left and then the right DLPFC improves cognitive function in patients with mild to moderate degree of AD. This improvement was maintained for 3 months. High frequency rTMS may be a useful addition to therapy for the treatment of AD.

In an era in which cardiovascular disease has become the main cause of death all over the world, diagnostic accuracy in identifying blood vessels has become particularly important. Vascular stenosis causes serious health risks by affecting blood flow, leading to conditions like heart attacks and strokes. Traditional diagnostic methods face challenges in terms of timeliness and accuracy. Our systematic review aims to critically assess the role of machine learning (ML) techniques in enhancing computed tomography angiography’s (CTA) diagnostic capabilities for vasoconstriction. This review followed the predetermined inclusion and exclusion criteria and focused on research articles published between January 2013 and October 2023 collected from databases such as PubMed, IEEE, Web of Science, and Scopus. Studies focus on multiphase CTA or dynamic CTA; papers do not use the ML; and papers not in English are removed. The risk of bias of included studies was evaluated using the QUADAS2 tool. The results were analyzed in tabular form using metrics such as accuracy, sensitivity, and specificity and examine variations in stenosis detection by anatomical regions. In our review, a total of 63 studies were identified as relevant. These studies included a variety of ML applications for identifying anatomical stenosis of the arteries in different anatomical areas. The findings highlighted a trend of high sensitivity and specificity in broader anatomical assessments, with nuanced variations observed in detailed segmental analysis. The review acknowledges limitations within the existing studies, including the retrospective nature of most studies and their limited scope in terms of patient diversity and center variation. Nonetheless, the implications of integrating ML in vascular stenosis detection via CTA are profound, suggesting a pivotal shift toward more accurate, efficient, and patient-centric diagnostic practices in cardiovascular care. Registration : The protocol for this systematic review and meta-analysis was registered on PROSPERO, with the registration number CRD420234603.

In this study, Artificial Neural Network (ANN) models were developed to predict the indirect tensile strength (ITS) of cold asphalt mixes (CAMs) incorporated with different industrial waste materials. Input variables were determined as variables including emulsion content, curing time, sludge ash content, additive type, and aggregate grading, which were investigated the influence on ITS of CAMs from 163 experimental mix designs. The ANN model structure was formulated, and the multilayer feedforward perceptron was trained, while the number of neurons in hidden layer was set to adjust the structure of the network. The neuron number analyze process shown that 5:3:1 structure selected as the final pattern. The efficient of the trained model is reasonably high with a prediction correlation coefficient (R) of 0.963, and it gives a low Mean Absolute Percentage Error (MAPE) equal to 11.9%. The sensitivity analysis also showed that the curing time and water content were the two highest parameters impacting the ITS, and the emulsion content and initial moisture content were the two lowest parameters influencing the ITS. The test error is increased as the neuron of hidden layer was selected as 4, 6, and 7, however the minimum error is seated as the neuron number was 3. We recommend that ANN-based methodologies show great potential in being reliable and efficient tools that can be used to emulate the mechanical responses of the CAMs tested in this study, as well as aid in designing more sustainable pavement materials.

The purpose of this study was to investigate the long-term efficacy of transcranial direct current stimulation (tDCS) in the neurorehabilitation of Alzheimer's disease (AD). Thirty-four AD patients were randomly assigned to three groups: anodal, cathodal, and sham tDCS. Stimulation was applied over the left dorsolateral prefrontal cortex for 25 min at 2 mA, daily for 10 days. Each patient was submitted to the following psychometric assessments: mini-mental state examination (MMSE) and Wechsler adult intelligence scale-third edition at base line, at the end of the 10th sessions and then at 1 and 2 months after the end of the sessions. Motor cortical excitability and the P300 event-related potential were assessed at baseline and after the last tDCS session. Significant treatment group × time interactions were observed for the MMSE and performance IQ of the WAIS. Post hoc comparisons showed that both anodal and cathodal tDCS (ctDCS) improved MMSE in contrast to sham tDCS. Whereas, this was only true for ctDCS in the performance IQ. Remarkably, tDCS also reduced the P300 latency, but had no effect on motor cortex excitability. Our findings reveal that repeated sessions of tDCS could not only improve cognitive function but also reduce the P300 latency, which is known to be pathologically increased in AD.

Background: Because there have been no epidemiological studies of stroke in Egypt, a community-based survey was conducted in the Assiut Governorate to estimate the prevalence and risk factors of stroke in our community. Methods: A three-phase door-to-door study was performed in which 6,498 participants were chosen by random sampling from 7 districts in Assiut (first phase). Out of this sample, 578 dropped out leaving 3,066 males (51.8%) and 2,854 females (48.2%). There were 3,660 (61.8%) urban residents and 2,260 (38.2%) from the rural community. In the second phase participants were screened using the questionnaire for stroke, while the third phase involved medical evaluation of all suspected cases, with diagnosis of stroke confirmed by evaluation of CT scans. The Mini Mental State Examination and Hamilton Depression Scale were evaluated for each patient. Results: 65 participants were identified as positive on the survey questionnaire, but only 57 patients were found to have stroke, giving a crude prevalence rate of 963/100,000 inhabitants with an age-adjusted local prevalence rate of 699.2/100,000 and an age-adjusted prevalence relative to the standard world population of 980.9/100,000. The prevalence among males was higher than females (1174/100,000 vs. 736/100,000) with a ratio 1.7:1. There was a significantly higher prevalence of ischemic (895/100,000) than hemorrhagic (68/100,000) stroke. Stroke prevalence was the same in rural and urban areas and in males and females. There was, however, a significantly higher prevalence in illiterate (2413/100,000) than literate participants (357/100,000). Forty-two patients (73.7%) had one or more risk factors for stroke, hypertension being the commonest (66%) and diabetes mellitus second (38.6%). Nine cases had poststroke dementia (15.8%) and 14 cases (24.6%) had mild depression. Conclusions: The overall prevalence rate of stroke is high, especially in older adults, men and illiterate individuals. A higher prevalence of ischemic than hemorrhagic stroke was recorded, with hypertension and diabetes mellitus being the commonest risk factors in our community.

Sir,--Your leader which appeared in Friday's issue was written in one of those rare, untrammelled moods when we sink our personal and racial pride in the cause of suffering humanity, when our nobler nature gets the better of sordid and sellfish motives and when the irresistible impulse is that of service and not of exploitation...

Baricitinib (BTB) is an orally administered Janus kinase inhibitor, therapeutically used for the treatment of rheumatoid arthritis. Recently it has also been approved for the treatment of COVID-19 infection. In this study, four different BTB-loaded lipids (stearin)-polymer (Poly(d,l-lactide-co-glycolide)) hybrid nanoparticles (B-PLN1 to B-PLN4) were prepared by the single-step nanoprecipitation method. Next, they were characterised in terms of physicochemical properties such as particle size, zeta potential (ζP), polydispersity index (PDI), entrapment efficiency (EE) and drug loading (DL). Based on preliminary evaluation, the B-PLN4 was regarded as the optimised formulation with particle size (272 ± 7.6 nm), PDI (0.225), ζP (−36.5 ± 3.1 mV), %EE (71.6 ± 1.5%) and %DL (2.87 ± 0.42%). This formulation (B-PLN4) was further assessed concerning morphology, in vitro release, and in vivo pharmacokinetic studies in rats. The in vitro release profile exhibited a sustained release pattern well-fitted by the Korsmeyer–Peppas kinetic model (R2 = 0.879). The in vivo pharmacokinetic data showed an enhancement (2.92 times more) in bioavailability in comparison to the normal suspension of pure BTB. These data concluded that the formulated lipid-polymer hybrid nanoparticles could be a promising drug delivery option to enhance the bioavailability of BTB. Overall, this study provides a scientific basis for future studies on the entrapment efficiency of lipid-polymer hybrid systems as promising carriers for overcoming pharmacokinetic limitations.

Cytochrome P450 (CYP450) is a group of enzymes that play an essential role in Phase I metabolism, with 57 functional genes classified into 18 families in the human genome, of which the CYP1, CYP2, and CYP3 families are prominent. Beyond drug metabolism, CYP enzymes metabolize endogenous compounds such as lipids, proteins, and hormones to maintain physiological homeostasis. Thus, dysregulation of CYP450 enzymes can lead to different endocrine disorders. Moreover, CYP450 enzymes significantly contribute to fatty acid metabolism, cholesterol synthesis, and bile acid biosynthesis, impacting cellular physiology and disease pathogenesis. Their diverse functions emphasize their therapeutic potential in managing hypercholesterolemia and neurodegenerative diseases. Additionally, CYP450 enzymes are implicated in the onset and development of illnesses such as cancer, influencing chemotherapy outcomes. Assessment of CYP450 enzyme expression and activity aids in evaluating liver health state and differentiating between liver diseases, guiding therapeutic decisions, and optimizing drug efficacy. Understanding the roles of CYP450 enzymes and the clinical effect of their genetic polymorphisms is crucial for developing personalized therapeutic strategies and enhancing drug responses in diverse patient populations.

Olmesartan medoxomil (OLM) is one of the prominent antihypertensive drug that suffers from low aqueous solubility and dissolution rate leading to its low bioavailability. To improve the oral bioavailability of OLM, a delivery system based on ethylcellulose (EC, a biobased polymer) nanosponges (NSs) was developed and evaluated for cytotoxicity against the A549 lung cell lines and antihypertensive potential in a rat model. Four OLM-loaded NSs (ONS1-ONS4) were prepared and fully evaluated in terms of physicochemical properties. Among these formulations, ONS4 was regarded as the optimized formulation with particle size (487 nm), PDI (0.386), zeta potential (ζP = −18.1 mV), entrapment efficiency (EE = 91.2%) and drug loading (DL = 0.88%). In addition, a nanosized porous morphology was detected for this optimized system with NS surface area of about 63.512 m2/g, pore volume and pore radius Dv(r) of 0.149 cc/g and 15.274 Å, respectively, measured by nitrogen adsorption/desorption analysis. The observed morphology plus sustained release rate of OLM caused that the optimized formulation showed higher cytotoxicity against A549 lung cell lines in comparison to the pure OLM. Finally, this system (ONS4) reduced the systolic blood pressure (SBP) significantly (p < 0.01) as compared to control and pure OLM drug in spontaneously hypertensive rats. Overall, this study provides a scientific basis for future studies on the encapsulation efficiency of NSs as promising drug carriers for overcoming pharmacokinetic limitations.