Effect of chloroquine pre-treatment on the metoclopramide's pharmacokinetics after their co-administration.

BACKGROUND: This study evaluated the pharmacokinetic interactions of orally administered chloroquine and metoclopramide. METHODS: The study employed a randomized and two-phase cross-over design with 4-week washout plan. Twelve healthy male volunteers were shortlisted according to the set criteria and were administered with metoclopramide 10 mg PO and chloroquine (a total of 1500 mg) at different intervals which were (500 mg at 0, 6, and 24 h). The concentration of chloroquine and metoclopramide in the blood samples was estimated using a validated HPLC-UV technique to affirm the maximum concentration (Cmax), time to reach Cmax (Tmax), and area under the curve (AUC). RESULTS: Cmax, T1/2, and AUC of metoclopramide were increased up to 20, 10, and 47.8%, respectively, by the concomitantly administering Chloroquine. Chloroquine-treated phase showed increased values of Cmax (ng/ml), AUC (ng.h/ml), and T½ (h), i.e. 41.35 ± 1.61, 504.12 ± 66.25, and 5.72 ± 2.63, as compared to that reference phase i.e. 34.52 ± 4.92, 341.14 ± 112.8, and 5.19 ± 1.14, respectively. CONCLUSIONS: Chloroquine was found to attenuate CYP2D6 activity in healthy Pakistani male volunteers. Hence, patients that are prescribed with metoclopramide or other CYP2D6-substrate drugs require a dose adjustment when administered with chloroquine.

A novel radial basis neural network for the Zika virus spreading model.

The motive of current investigations is to design a novel radial basis neural network stochastic structure to present the numerical representations of the Zika virus spreading model (ZVSM). The mathematical ZVSM is categorized into humans and vectors based on the susceptible S(q), exposed E(q), infected I(q) and recovered R(q), i.e., SEIR. The stochastic performances are designed using the radial basis activation function, feed forward neural network, twenty-two numbers of neurons along with the optimization of Bayesian regularization in order to solve the ZVSM. A dataset is achieved using the explicit Runge-Kutta scheme, which is used to reduce the mean square error (MSE) based on the process of training for solving the nonlinear ZVSM. The division of the data is categorized into training, which is taken as 78 %, while 11 % for both authentication and testing. Three different cases of the nonlinear ZVSM have been taken, while the scheme's correctness is performed through the matching of the results. Furthermore, the reliability of the scheme is observed by applying different performances of regression, MSE, error histograms and state transition.

Cancer Treatment Using Nanofibers: A Review.

Currently, the number of patients with cancer is expanding consistently because of a low quality of life. For this reason, the therapies used to treat cancer have received a lot of consideration from specialists. Numerous anticancer medications have been utilized to treat patients with cancer. However, the immediate utilization of anticancer medicines leads to unpleasant side effects for patients and there are many restrictions to applying these treatments. A number of polymers like cellulose, chitosan, Polyvinyl Alcohol (PVA), Polyacrylonitrile (PAN), peptides and Poly (hydroxy alkanoate) have good properties for the treatment of cancer, but the nanofibers-based target and controlled drug delivery system produced by the co-axial electrospinning technique have extraordinary properties like favorable mechanical characteristics, an excellent release profile, a high surface area, and a high sponginess and are harmless, bio-renewable, biofriendly, highly degradable, and can be produced very conveniently on an industrial scale. Thus, nanofibers produced through coaxial electrospinning can be designed to target specific cancer cells or tissues. By modifying the composition and properties of the nanofibers, researchers can control the release kinetics of the therapeutic agent and enhance its accumulation at the tumor site while minimizing systemic toxicity. The core-shell structure of coaxial electrospun nanofibers allows for a controlled and sustained release of therapeutic agents over time. This controlled release profile can improve the efficacy of cancer treatment by maintaining therapeutic drug concentrations within the tumor microenvironment for an extended period.

A Comprehensive Review of Hepatitis B Vaccine Nonresponse and Associated Risk Factors.

Hepatitis B virus (HBV) infection remains a significant global health concern worldwide, contributing to high rates of mortality and morbidity, including chronic hepatitis B, cirrhosis, and hepatocellular carcinoma (HCC). Universal vaccination programs have significantly reduced the rate of HBV transmission; however, a subset of individuals fail to develop a protective immune response following vaccination and are termed nonresponders. A comprehensive search strategy using the PubMed, Google Scholar, and Web of Science databases was employed to search for relevant studies using keywords including "hepatitis B vaccine", "vaccine nonresponse", "immunogenicity", "immune response to the hepatitis B vaccine", and "associated risk factors". Factors influencing the vaccine's response include demographic factors, such as age and sex, with increased nonresponse rates being observed in older adults and males. Obesity, smoking, and alcohol consumption are lifestyle factors that decrease the vaccine response. Medical conditions, including diabetes, chronic kidney and liver diseases, HIV, celiac disease, and inflammatory bowel disease, affect the vaccine response. Major histocompatibility complex (MHC) haplotypes and genetic polymorphisms linked to immune regulation are genetic factors that further influence the vaccine's effectiveness. To reduce the global burden of hepatitis B infection, it is essential to understand these factors to improve vaccine effectiveness and develop individualized vaccination strategies.

Evaluating the efficacy of ubiquinol in heart failure patients: a systematic review and meta-analysis.

Aim: We aim to analyze past literature to evaluate the efficacy of coenzyme Q10 (CoQ-10) in the population with heart failure (HF). Methods: A systematic literature search was conducted through MEDLINE (via PubMed) and Cochrane Library. The outcomes analyzed were a reduction in HF-related mortality, an improvement in exercise capacity, and the left ventricular ejection fraction (LVEF). Results: Among 16 studies, CoQ-10 significantly reduced HF-related mortality by 40% and improved exercise capacity in patients with HF, but demonstrated no significant difference in LVEF however, the potential of its efficacy on LVEF could not be ruled out. Conclusion: CoQ-10 significantly enhances exercise capacity and reduces HF-related mortality; however, its impact on patients with reduced LVEF requires further investigation.

[Box: see text].

Nanomaterial-based sensors for microbe detection: a review.

Airborne microorganisms pose a significant health threat, causing various illnesses. Traditional detection methods are often slow and complex. This review highlights the potential of nanomaterial-based biosensors, particularly colorimetric sensors, for rapid and on-site detection of airborne microbes. Colorimetric sensors offer real-time visual detection without complex instrumentation. We explore the integration of these sensors with Lab-on-a-Chip technology using PDMS microfluidics. This review also proposes a novel PDMS-based colorimetric biosensor for real-time detection of airborne microbes. The sensor utilizes a color change phenomenon easily observable with the naked eye, simplifying analysis and potentially enabling point-of-care applications.

Glycolipids biosurfactants production using low-cost substrates for environmental remediation: progress, challenges, and future prospects.

The production of renewable materials from alternative sources is becoming increasingly important to reduce the detrimental environmental effects of their non-renewable counterparts and natural resources, while making them more economical and sustainable. Chemical surfactants, which are highly toxic and non-biodegradable, are used in a wide range of industrial and environmental applications harming humans, animals, plants, and other entities. Chemical surfactants can be substituted with biosurfactants (BS), which are produced by microorganisms like bacteria, fungi, and yeast. They have excellent emulsifying, foaming, and dispersing properties, as well as excellent biodegradability, lower toxicity, and the ability to remain stable under severe conditions, making them useful for a variety of industrial and environmental applications. Despite these advantages, BS derived from conventional resources and precursors (such as edible oils and carbohydrates) are expensive, limiting large-scale production of BS. In addition, the use of unconventional substrates such as agro-industrial wastes lowers the BS productivity and drives up production costs. However, overcoming the barriers to commercial-scale production is critical to the widespread adoption of these products. Overcoming these challenges would not only promote the use of environmentally friendly surfactants but also contribute to sustainable waste management and reduce dependence on non-renewable resources. This study explores the efficient use of wastes and other low-cost substrates to produce glycolipids BS, identifies efficient substrates for commercial production, and recommends strategies to improve productivity and use BS in environmental remediation.

Initial Experience of Robot-Assisted Surgeries.

OBJECTIVE: To present initial experience with the first 100 cases of robotic-assisted surgery by the Department of General Surgery. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Department of Surgery, National Hospital and Medical Centre, Lahore, Pakistan, from May 2022 to August 2023. METHODOLOGY: Demographic and postoperative details of the first 100 patients to undergo robotic-assisted surgery by the Department of General Surgery were reviewed. Prospective data were collected from the hospital information database as well as the CMR database. The data collected in the hospital database included the patients' age, diagnoses, genders, complications during hospital stay as well as 90-day readmission, morbidity, and mortality. Data collected by CMR via Versius robotic surgery console or internal databases included operative minutes using the console. RESULTS: The average age of patients undergoing robotic surgery was 44.26 ± 14.08 years. Cholecystectomy (78%) was the most commonly performed robotic-assisted procedure. Only one patient had blood loss of more than 100ml. There was no postoperative complication, readmission or mortality during the study period. CONCLUSION: With proper patient selection, robotic-assisted surgery is safe and feasible even in low- middle-income countries (LMICs). KEY WORDS: Robotic-assisted surgery, Pakistan, Initial experience, Outcomes, Versius.

Cross-Cultural Adaptation and Psychometric Validation of the Quality of Life Index Among Hausa-Speaking People with Spinal Cord Injury in Northwest Nigeria.

Background: Quality of life (QoL) is an important outcome that is used to measure the success of healthcare interventions. Valid and reliable instruments are required to assess QoL. Hence, we conducted this study to adapt and validate the QoL Index (QLI) among Hausa-speaking people with spinal cord injury (SCI) in northwest Nigeria. Method: Using the International Society for Pharmacoeconomic and Outcome Research principles of good practice and the consensus-based standards for the selection of health measurement instruments guidelines, the QLI-SCI version was translated into Hausa language and tested for content validity, internal consistency, and test-retest reliability among people with SCI in northwest Nigeria. Result: The Hausa QLI (HQLI) demonstrated good content validity (CVI = 92.18%), internal consistency (Cronbach's alpha = 0.855), and test-retest reliability (ICC =0.949 [95% CI, 0.916-0.969]). Conclusion: The HQLI can be deployed to assess QoL among Hausa-speaking people with SCI, thus promoting robust measurement of QoL in an SCI population.

A Comparative Study of the Graston Technique and Alfredson Protocol in the Management of Achilles Tendinopathy.

BACKGROUND AND OBJECTIVES: The Achilles tendon, the largest and strongest tendon in the human body, is frequently injured by overuse; this condition is known as Achilles tendinopathy (AT). It serves as a link between the heel bone and the calf muscles and is necessary for motions, such as walking, sprinting, and jumping. Evidence is presented to support the efficacy of the Graston technique and Alfredson protocol for pain reduction and improvement of function and calf muscle strength. The objective of this study is to compare the efficacy of the Graston technique versus the Alfredson protocol in patients with AT. Methods and data collection: After obtaining approval from the ethical review board of the Rawalpindi Medical University, all patients fulfilling the inclusion criteria are divided into two groups, A and B, by generating random identity numbers using Microsoft Excel for allocation. Group A comprises patients who undergo treatment with the Graston technique as conventional therapy with Alfredson protocol (12-week calf muscle eccentric exercises), while those in group B follow a Graston technique with sole heel lift. Individuals in the eccentric exercises group follow an Alfredson method-based 12-week eccentric exercise plan for their leg muscles. The workouts need to be done twice a day, seven days a week for 12 weeks. The plan includes two exercises: the first done with the knee straightened to work the gastrocnemius and the second done with the knee bent to work the soleus. Three sets of 15 repetitions with no rest interval for each exercise are completed twice a day on the affected limb to yield functional improvement. RESULTS: The results showed that both the Alfredson protocol and the Graston technique were effective in managing AT symptoms. The study involved dividing 32 participants into two groups who received either treatment for four weeks. The main way to measure improvement was a score called the Villalta-Scanlon Achilles Tendonitis Index score. In both groups, these scores showed significant improvement (with a p-value less than 0.001, which means that the results are very statistically significant). For Group A (who received the Alfredson protocol), the average Villalta-Scanlon Achilles Tendonitis Index score before treatment was 29.25. This score increased to 31.25 at mid-treatment and 34.38 after the full four weeks of treatment. Group B (who received the Graston technique) started with an average Villalta-Scanlon Achilles Tendonitis Index score of 22.94. Their scores also increased throughout the treatment, reaching 34.94 at mid-treatment and 42.88 after four weeks. These findings provide evidence that both treatments can improve AT symptoms, with some suggestions that the Graston technique might be even more effective based on the higher average Villalta-Scanlon Achilles Tendonitis Index scores after treatment. CONCLUSIONS: The Graston technique shows promising results, particularly in the mid- and post-treatment phases, indicating its potential efficacy in comparison to the Alfredson protocol in the treatment of AT.

Spatial distribution of physicochemical parameters and drinking and irrigation water quality indices in the Jhelum River, Pakistan.

Sustainable management of river systems is a serious concern, requiring vigilant monitoring of water contamination levels that could potentially threaten the ecological community. This study focused on the evaluation of water quality in the Jhelum River (JR), Azad Jammu and Kashmir, and northern Punjab, Pakistan. To achieve this, 60 water samples were collected from various points within the JR Basin (JRB) and subjected to a comprehensive analysis of their physicochemical parameters. The study findings indicated that the concentrations of physicochemical parameters in the JRB water remained within safety thresholds for both drinking and irrigation water, as established by the World Health Organization and Pakistan Environmental Protection Agency. These physicochemical parameters refer to various chemical and physical characteristics of the water that can have implications for both human health (drinking water) and agricultural practices (irrigation water). The spatial variations throughout the river course distinguished between the upstream, midstream, and downstream sections. Specifically, the downstream section exhibited significantly higher values for physicochemical parameters and a broader range, highlighting a substantial decline in its quality. Significant disparities in mean values and ranges were evident, particularly in the case of nitrates and total dissolved solids, when the downstream section was compared with its upstream and midstream counterparts. These variations indicated a deteriorating downstream water quality profile, which is likely attributable to a combination of geological and anthropogenic influences. Despite the observed deterioration in the downstream water quality, this study underscores that the JRB within the upper Indus Basin remains safe and suitable for domestic and agricultural purposes. The JRB was evaluated for various irrigation water quality indices. The principal component analysis conducted in this study revealed distinct covariance patterns among water quality variables, with the first five components explaining approximately 79% of the total variance. Recommending the continued utilization of the JRB for irrigation, we advocate for the preservation and enhancement of water quality in the downstream regions.

Novel acyl hydrazide derivatives of polyhydroquinoline as potent anti-diabetic and anti-glycating agents: Synthesis, in vitro α-amylase, α-glucosidase inhibition and anti-glycating activity with molecular docking insights.

In this study, eleven novel acyl hydrazides derivative of polyhydroquinoline were synthesized, characterized and screened for their in vitro anti-diabetic and anti-glycating activities. Seven compounds 2a, 2d, 2i, 2 h, 2j, 2f, and 2 g exhibited notable α-amylase inhibitory activity having IC50 values from 3.51 ± 2.13 to 11.92 ± 2.30 µM. Similarly, six compounds 2d, 2f, 2 h, 2i, 2j, and 2 g displayed potent α-glucosidase inhibitory activity compared to the standard acarbose. Moreover, eight derivatives 2d, 2 g, 2f, 2j, 2a, 2i, 2 g, and 2e showed excellent anti-glycating activity with IC50 values from 6.91 ± 2.66 to 15.80 ± 1.87 µM when compared them with the standard rutin (IC50 = 22.5 ± 0.90 µM). Molecular docking was carried out to predict the binding modes of all the compounds with α-amylase and α-glucosidase. The docking analysis revealed that most of the compounds established strong interactions with α-amylase and α-glucosidase. All compounds fitted well into the binding pockets of α-amylase and α-glucosidase. Among all compounds 2a and 2f were most potent based on docking score -8.2515 and -7.3949 against α-amylase and α-glucosidase respectively. These results hold promise for the development of novel candidates targeted at controlling postprandial glucose levels in individuals with diabetes.

Therapeutic Potential of Combined Herbal Medicine and Electroacupuncture in Mild Cognitive Impairment Through Cytokine Modulation: An Observational Study.

Purpose: We aimed to investigate the efficacy of a combined herbal formula and electroacupuncture (EA) for mild cognitive impairment (MCI), a neurodegenerative disease leading to dementia, and its underlying mechanisms of action. Patients and Methods: This was a prospective open-label observational pilot study at Daejeon Korean Medicine Hospital of Daejeon University in South Korea from March 2022 to March 2023. We included six Korean patients (50% male) aged ≥ 45 years and < 85 years with MCI, a clinical dementia rating score of 0.5, and a Montreal Cognitive Assessment-Korea (MoCA-K) score ≤ 22. The exclusion criterion was impaired cognitive function. Patients received combined therapy, including a herbal formula and EA, for 12-24 weeks. We prescribed the herbal formulas Gamiguibi-tang, Yukmijihwang-tang, and Banhasasim-tang to the patients for at least 70% of the treatment period, in combination with EA. Moreover, we investigated changes in cognitive and cognition-related symptoms and cytokine expression in the blood following combined traditional medicine therapy. At baseline and after 12 and 24 weeks, we administered the MoCA-K and cognitive-related questionnaires. We analyzed network pharmacology to reflect the herbal formula intervention mechanism comprehensively. Results: The median score [interquartile range] of MoCA-K at baseline was 19.5 [16.0, 22.0], which improved significantly (24.5 [24.0, 26.0], p < 0.01) over 24 weeks following combined therapy. We obtained no significant conclusion regarding cytokine changes due to the small sample size. In network pharmacology, we analyzed the brain, head, heart, peripheral nerves, peripheral nervous system, and pancreas as the enriched organs from the common targets of the three herbal formulas. Conclusion: Combined herbal medicine and EA improved cognitive function in patients with MCI. We assume the underlying mechanism of herbal formulas to be antioxidative and anti-inflammatory changes in cytokine expression. Combined traditional medicine has potential therapeutic application in preventing MCI progression to dementia.

This was a single-centered study focusing on the therapeutic effect of combined herbal medicine and electroacupuncture in patients with mild cognitive impairment, including a small number of participants, a relatively long treatment intervention of 12 weeks, and a follow-up assessment of 24 weeks. The intervention was a combination of a herbal formula and electroacupuncture treatment customized for each participant. The blood cytokine analyses of the participants were compared with the network analysis of the predicted target organs and pathways for the herbal formulas administered. Because each participant was not given the exact same intervention, we were unable to identify the specific treatment that produced the predicted effect. The observational study design of the study limited the ability to accurately assess causation between intervention and outcome. However, combined traditional medicine has potential therapeutic application in preventing mild cognitive impairment progression to dementia.

Coping strategies of internally displaced persons and the host community in a region of armed conflict: A cross-sectional study.

BACKGROUND: Conflict leads to the displacement of people, making it more difficult for them to cope with increasing stress. In war-affected regions, people use different strategies to cope with their stress. This study examines the coping strategies of internally displaced persons (IDPs) and those in host communities in war zones. METHODS: People living in the IDP camp and host communities in Maiduguri, Nigeria were recruited using a convenient sampling strategy. A 28-item Hausa version of the Brief COPE Scale wasused for data collection. Data were analyzed using linear regression and presented as unstandardized beta (B) and standard error (SE). RESULTS: A total of 562 participants were recruited (IDPs, n = 281; and the host communities, n = 281). Problem- and emotion-focused coping strategies were identified as the most common approaches used in host communities; however, dysfunctional strategies were morecommon among the IDPs. Age (younger or older adulthood) was identified as a predictor forthe use of emotion-, problem-, and dysfunctional-focused coping strategies. CONCLUSION: Host communities were more likely to use a problem-and emotion-focused approach to coping, while IDPs were more likely to use dysfunctional strategies. Location and demographic factors (being single, aged 18-29years, >50 years and older) also influenced coping.

Synthesis, molecular docking evaluation for LOX and COX-2 inhibition and determination of in-vivo analgesic potentials of aurone derivatives.

In the current study, seven (7) aurone derivatives (ADs) were synthesized and employed to in-vitro LOX and COX-2 assays, in-vivo models of acetic acid-induced mice writhing, formalin-induced mice paw licking and tail immersion test to evaluate their analgesic potential at the doses of 10 mg and 20 mg/kg body weight. Molecular docking was performed to know the active binding site at both LOX and COX-2 as compared to standard drugs. Among the ADs, 2-(3,4-dimethoxybenzylidene)benzofuran-3(2H)-one (WE-4)possessed optimal LOX and COX-2 inhibitory strength (IC50=0.30 µM and 0.22 µM) as compared to standard (ZileutonIC50 = 0.08 µM, CelecoxibIC50 = 0.05 µM). Similarly in various pain models compound WE-4 showed significantly (p < 0.05) highest percent analgesic potency as compared to control at a dose of 20 mg/kg i.e. 77.60 % analgesic effect in acetic acid model, 49.97 % (in Phase-1) and 70.93 % (inPhase-2) analgesic effect in formalin pain model and 74.71 % analgesic response in tail immersion model. By the administration of Naloxone, the tail flicking latencies were reversed (antagonized) in all treatments. The WE-4 (at 10 mg/kg and 20 mg/kg) was antagonized after 90 min from 11.23 ± 0.93 and 13.41 ± 1.21 to 5.30 ± 0.48 and 4.80 ± 0.61 respectively as compared to standard Tramadol (from 17.74 ± 1.33 to 3.70 ± 0.48), showing the opiodergic receptor involvement. The molecular docking study of ADs revealed that WE-4 had a higher affinity for LOX and COX-2 with docking scores of -4.324 and -5.843 respectively. As a whole, among the tested ADs, compound WE-4 demonstrated excellent analgesic effects that may have been caused by inhibiting the LOX and COX-2 pathways.