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Article: CYP3A5 Polymorphisms Leading to Tacrolimus Toxicity Following an Adult Renal Transplant.

Alotaibi, Nouf

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia

2024 Volume 34, Issue 3, Page(s) 250–253

Abstract: Tacrolimus is one of the calcineurin inhibitors used for maintaining immuno-suppression in thoracic and abdominal transplantations including heart, lung, liver, intestine, pancreas, and renal transplants. It has a narrow therapeutic window requiring ... ...

Abstract	Tacrolimus is one of the calcineurin inhibitors used for maintaining immuno-suppression in thoracic and abdominal transplantations including heart, lung, liver, intestine, pancreas, and renal transplants. It has a narrow therapeutic window requiring therapeutic drug monitoring (TDM). Genetic polymorphism in the expression of cytochrome P3A5 enzyme plays a significant role in the bioavailability of tacrolimus in patients, leading to toxicity or rejection. In this case, we studied a renal transplant patient who received a standard dose of tacrolimus and experienced toxicity related to the poor expression of cytochrome P450 3A5 (CYP3A5), which required the withholding of tacrolimus and cutting the dose for several days with more frequent TDM. Similar cases have been reported before, yet there is no consensus on the appropriate dosage. The projected cost of additional TDM and hospitalization significantly exceeds the one-time cost of genetic CYP3A5 testing. In high-risk renal transplant recipients, pharmacogenetic testing must be considered to cut the time to limit TDM, prevent extended hospitalization, and reduce the total cost of transplantation.
MeSH term(s)	Adult ; Humans ; Tacrolimus/therapeutic use ; Cytochrome P-450 CYP3A/genetics ; Cytochrome P-450 CYP3A/metabolism ; Kidney Transplantation/adverse effects ; Immunosuppressive Agents/adverse effects ; Polymorphism, Genetic ; Genotype ; Polymorphism, Single Nucleotide
Chemical Substances	Tacrolimus (WM0HAQ4WNM) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; Immunosuppressive Agents ; CYP3A5 protein, human (EC 1.14.14.1)
Language	English
Publishing date	2024-01-17
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	1379955-1
ISSN	1319-2442
ISSN	1319-2442
DOI	10.4103/1319-2442.393998
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Article: Formulation and evaluation of chitosan-based nanogel for oral delivery of diosmin.

Ali Mujtaba, Mohammed / M Alotaibi, Nawaf

Pakistan journal of pharmaceutical sciences

2023 Volume 36, Issue 2, Page(s) 535–540

Abstract: The bioactive flavonoid diosmin (DSN) has a variety of biological activities, excellent therapeutic activity, however, it has a number of biopharmaceutical problems that limit its advantages. The present study aims to develop chitosan-based nanogels (NGs) ...

Abstract	The bioactive flavonoid diosmin (DSN) has a variety of biological activities, excellent therapeutic activity, however, it has a number of biopharmaceutical problems that limit its advantages. The present study aims to develop chitosan-based nanogels (NGs) as drug-delivery platforms for DSN and characterize them using physicochemical methods. DSN-loaded NGs were prepared using the ionic gelation method and particle size (PS), poly-dispersity index (PDI), zeta potential (ZP), loading efficiency (LE) and loading capacity (LC) of 113.07±12.62nm, 0.266±0.08, 22.32± 0.56 mV, 81.56±2.65% and 10.25±1.43% were obtained, respectively. Transmission electron microscopy analysis of DSN-loaded NGs also revealed that the PS ranged from 100 to 200nm, which is comparable to the outcomes of the dynamic light scattering technique. The NGs swelled in pH 6.8 and pH 7.4 buffers and was easily eroded at pH 1.2 and pH 4.5. DSN was released from NGs in acidic buffers by a Fickian process and this release was followed by both swelling and erosion. According to stability experiments, the PS, ZP and PDI at 25oC and 40oC did not significantly change after 90 days. In conclusion, the NGs system proved very effective at delivering DSN orally.
MeSH term(s)	Nanogels ; Chitosan/chemistry ; Diosmin/chemistry ; Drug Carriers/chemistry ; Particle Size ; Nanoparticles/chemistry
Chemical Substances	polyethylene glycol polyethyleneimine nanogel ; Nanogels ; Chitosan (9012-76-4) ; Diosmin (7QM776WJ5N) ; Drug Carriers
Language	English
Publishing date	2023-08-02
Publishing country	Pakistan
Document type	Journal Article
ZDB-ID	885131-1
ISSN	1011-601X
ISSN	1011-601X
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Article ; Online: Efficacy of splinting the wrist and metacarpophalangeal joints for the treatment of Carpal tunnel syndrome: an assessor-blinded randomised controlled trial.

Nadar, Mohammed Sh / Alotaibi, Naser / Manee, Fahad

BMJ open

2023 Volume 13, Issue 11, Page(s) e076961

Abstract: Objectives: To compare the efficacy of a traditional cock-up splint, which supports the wrist only, with a modified splint that supports the wrist and the metacarpophalangeal (MCP) joints of the medial four digits in the treatment of carpal tunnel ... ...

Abstract	Objectives: To compare the efficacy of a traditional cock-up splint, which supports the wrist only, with a modified splint that supports the wrist and the metacarpophalangeal (MCP) joints of the medial four digits in the treatment of carpal tunnel syndrome (CTS). Design: An assessor-blind randomised controlled trial. Setting: Hospital-based hand therapy clinics. Participants: Fifty-nine adults with mild-to-moderate CTS were randomly assigned to wear a wrist splint (control group) or an MCP splint (intervention group) for 6 weeks. Outcome measures: The standardised outcome measures used included grip and pinch strength, the static two-point discrimination test, Phalen's manoeuvre test, Tinel's sign and the Boston CTS Questionnaire. Results: Both groups improved significantly from splint use in some clinical features. The wrist splint and the MCP splint groups had significant improvements in lateral pinch strength (p=0.032 and p=0.002, respectively), two-point discrimination of the thumb (p=0.003 and p=0.041, respectively), two-point discrimination of the index (p=0.035 and p=0.023, respectively) and the Phalen's manoeuvre symptoms (p=0.025 and p=0.002, respectively). The MCP splint group had additional improvements over the wrist splint group in tip pinch (p=0.012) and Palmar pinch (p=0.011) strength. Conclusion: Splinting is a practical and effective intervention option for improving the symptoms of CTS. A wrist splint that incorporates the MCP joints is more effective than the traditional wrist-only splint, with long-lasting improvements that remained consistent after 6 months of the splint intervention. Using the more effective MCP splint may consequently reduce disability, facilitate return to work and lower the associated costs. Trial registration number: ISRCTN13189602.
MeSH term(s)	Adult ; Humans ; Carpal Tunnel Syndrome/therapy ; Wrist ; Occupational Therapy ; Hand Strength ; Metacarpophalangeal Joint ; Treatment Outcome
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2023-076961
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Article ; Online: Classification of Autism Spectrum Disorder From EEG-Based Functional Brain Connectivity Analysis.

Alotaibi, Noura / Maharatna, Koushik

Neural computation

2021 Volume 33, Issue 7, Page(s) 1914–1941

Abstract: Autism is a psychiatric condition that is typically diagnosed with behavioral assessment methods. Recent years have seen a rise in the number of children with autism. Since this could have serious health and socioeconomic consequences, it is imperative ... ...

Abstract	Autism is a psychiatric condition that is typically diagnosed with behavioral assessment methods. Recent years have seen a rise in the number of children with autism. Since this could have serious health and socioeconomic consequences, it is imperative to investigate how to develop strategies for an early diagnosis that might pave the way to an adequate intervention. In this study, the phase-based functional brain connectivity derived from electroencephalogram (EEG) in a machine learning framework was used to classify the children with autism and typical children in an experimentally obtained data set of 12 autism spectrum disorder (ASD) and 12 typical children. Specifically, the functional brain connectivity networks have quantitatively been characterized by graph-theoretic parameters computed from three proposed approaches based on a standard phase-locking value, which were used as the features in a machine learning environment. Our study was successfully classified between two groups with approximately 95.8% accuracy, 100% sensitivity, and 92% specificity through the trial-averaged phase-locking value (PLV) approach and cubic support vector machine (SVM). This work has also shown that significant changes in functional brain connectivity in ASD children have been revealed at theta band using the aggregated graph-theoretic features. Therefore, the findings from this study offer insight into the potential use of functional brain connectivity as a tool for classifying ASD children.
MeSH term(s)	Autism Spectrum Disorder ; Brain/diagnostic imaging ; Child ; Electroencephalography ; Humans ; Machine Learning ; Support Vector Machine
Language	English
Publishing date	2021-08-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1025692-1
ISSN	1530-888X ; 0899-7667
ISSN (online)	1530-888X
ISSN	0899-7667
DOI	10.1162/neco_a_01394
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Article ; Online: Global Epidemiology, Clinical Features, Diagnosis and Current Therapeutic Novelties in Migraine Therapy and their Prevention: A Narrative Review.

Ali, Mohammad Daud / Gayasuddin Qur, Fehmida / Alam, Md Sarfaraz / M Alotaibi, Nawaf / Mujtaba, Md Ali

Current pharmaceutical design

2024 Volume 29, Issue 41, Page(s) 3295–3311

Abstract: Introduction: The current article reviews the latest information on epidemiology, clinical features, diagnosis, recent advancements in clinical management, current therapeutic novelties, and the prevention of migraines. In a narrative review, all ... ...

Abstract	Introduction: The current article reviews the latest information on epidemiology, clinical features, diagnosis, recent advancements in clinical management, current therapeutic novelties, and the prevention of migraines. In a narrative review, all studies as per developed MeSH terms published until February 2023, excluding those irrelevant, were identified through a PubMed literature search. Methods: Overall, migraine affects more than a billion people annually and is one of the most common neurological illnesses. A wide range of comorbidities is associated with migraines, including stress and sleep disturbances. To lower the worldwide burden of migraine, comprehensive efforts are required to develop and enhance migraine treatment, which is supported by informed healthcare policy. Numerous migraine therapies have been successful, but not all patients benefit from them. Results: CGRP pathway-targeted therapy demonstrates the importance of translating mechanistic understanding into effective treatment. In this review, we discuss clinical features, diagnosis, and recently approved drugs, as well as a number of potential therapeutic targets, including pituitary adenylate cyclase-activating polypeptide (PACAP), adenosine, opioid receptors, potassium channels, transient receptor potential ion channels (TRP), and acid-sensing ion channels (ASIC). Conclusion: In addition to providing more treatment options for improved clinical care, a better understanding of these mechanisms facilitates the discovery of novel therapeutic targets.
MeSH term(s)	Humans ; Acid Sensing Ion Channels ; Adenosine ; Migraine Disorders/diagnosis ; Migraine Disorders/drug therapy ; Migraine Disorders/epidemiology ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Potassium Channels
Chemical Substances	Acid Sensing Ion Channels ; Adenosine (K72T3FS567) ; Pituitary Adenylate Cyclase-Activating Polypeptide ; Potassium Channels
Language	English
Publishing date	2024-01-17
Publishing country	United Arab Emirates
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/0113816128266227231205114320
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Article: A Rare Case of Chronic Rhinosinusitis With Elevated Levels of Immunoglobulin G4.

Almohammadi, Hassan / Almslam, Maha S / Almslam, Ahmed S / Alotaibi, Naif

Cureus

2023 Volume 15, Issue 7, Page(s) e42246

Abstract: Chronic rhinosinusitis is a condition characterized by inflammation of the paranasal sinuses causing several symptoms, including facial pain, anosmia, nasal drainage, and obstruction for a minimal duration of three months. It is a commonly occurring ... ...

Abstract	Chronic rhinosinusitis is a condition characterized by inflammation of the paranasal sinuses causing several symptoms, including facial pain, anosmia, nasal drainage, and obstruction for a minimal duration of three months. It is a commonly occurring disease and is diagnosed through direct visualization or the detection of inflammation on a CT scan. A mucosal tissue biopsy typically reveals stromal fibrosis and an increase in submucosal glands, and infiltration of mixed mononuclear cells, neutrophils, and eosinophils may also be present but typically makes up less than 10% of the total cells. T helper type 2 releasing cytokines, interleukins (IL-5 and IL-13), as well as histamine, are frequently found in high concentrations in polyp tissue. We report a case of rare chronic rhinosinusitis. The patient's specimen shows a very high number of immunoglobulin G4 (IgG4)-positive plasma cells.
Language	English
Publishing date	2023-07-21
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.42246
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Article ; Online: Optimizing the generation of mature bone marrow-derived dendritic cells in vitro: a factorial study design.

Alotaibi, Najla / Aldahlawi, Alia / Zaher, Kawther / Basingab, Fatemah / Alrahimi, Jehan

Journal, genetic engineering & biotechnology

2023 Volume 21, Issue 1, Page(s) 144

Abstract: Background: Factorial design is a simple, yet elegant method to investigate the effect of multiple factors and their interaction on a specific response simultaneously. Hence, this type of study design reaches the best optimization conditions of a ... ...

Abstract	Background: Factorial design is a simple, yet elegant method to investigate the effect of multiple factors and their interaction on a specific response simultaneously. Hence, this type of study design reaches the best optimization conditions of a process. Although the interaction between the variables is widely prevalent in cell culture procedures, factorial design per se is infrequently utilized in improving cell culture output. Therefore, we aim to optimize the experimental conditions for generating mature bone marrow-derived dendritic cells (BMDCs). Two different variables were investigated, including the concentrations of the inducing factors and the starting density of the bone marrow mononuclear cells. In the current study, we utilized the design of experiments (DoE), a statistical approach, to systematically assess the impact of factors with varying levels on cell culture outcomes. Herein, we apply a two-factor, two-level (2 Results: The current study showed that the highest total viable cells and cells yield obtained were in cell group seeded at 2 × 10 Conclusion: The analysis of this study indicates a substantial interaction between cytokines combinations and cell densities on BMDC maturation. However, higher cell density is not associated with optimizing DC maturation. Notably, applying DoE in bioprocess designs increases experimental efficacy and reliability while minimizing experiments, time, and process costs.
Language	English
Publishing date	2023-11-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2637420-1
ISSN	2090-5920 ; 1687-157X ; 2090-5920
ISSN (online)	2090-5920
ISSN	1687-157X ; 2090-5920
DOI	10.1186/s43141-023-00597-4
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Article ; Online: Pharmacists' communication skills with deaf and hard of hearing patients: A needs assessment.

Al Aloola, Noha / Alanazi, Maram / Alotaibi, Norah / Alwhaibi, Monira

PloS one

2023 Volume 18, Issue 6, Page(s) e0286537

Abstract: Objectives: Assess the Saudi pharmacists' perceptions of their responsibilities toward deaf and hard-of-hearing (DHH) patients, their current practices, and their need for communication skills training.: Study design: A prospective cross-sectional ... ...

Abstract	Objectives: Assess the Saudi pharmacists' perceptions of their responsibilities toward deaf and hard-of-hearing (DHH) patients, their current practices, and their need for communication skills training. Study design: A prospective cross-sectional study. Methods: Pharmacist and deaf communication questionnaire (PDCQ), a newly structured, validated, pilot-tested, and self-administered online questionnaire, was used to collect data. A total of 303 pharmacists working in the Saudi community and outpatient pharmacies participated in the study. Data were analyzed using SPSS and descriptive statistics were used to describe the study findings. These included Mean ± standard deviation (SD), frequency, and Chi-square tests. Results: Most pharmacists perceived that DHH patients had difficulty correctly understanding their medication instructions. Writing was the most common method used for communication, whereas the unavailability of interpreters and the low reading levels of these patients were the highest barriers to communication. Moreover, most pharmacists believed that they should be skilled at communicating with DHH patients. However, many pharmacists felt that they are not well prepared to communicate with these patients. Conclusion: This research highlights the poor skills, low confidence and low knowledge Saudi pharmacists have about their legal obligations towards DHH patients. In addition, there is paucity of sufficient resources to help pharmacists improve their communication with such patients.
MeSH term(s)	Humans ; Needs Assessment ; Cross-Sectional Studies ; Persons With Hearing Impairments ; Pharmacists ; Prospective Studies ; Hearing Loss ; Communication
Language	English
Publishing date	2023-06-29
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0286537
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Article ; Online: Rectal roflumilast improves trinitrobenzenesulfonic acid-induced chronic colitis in rats.

Shaikh-Omar, A / Murad, H A / Alotaibi, N M

Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas

2022 Volume 55, Page(s) e11877

Abstract: Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via ... ...

Abstract	Roflumilast, a highly selective oral phosphodiesterase IV inhibitor, exerts anti-inflammatory and anti-fibrotic effects. Oral roflumilast causes gastrointestinal side effects, especially vomiting, which could be reduced by administering roflumilast via off-label routes. Inhaled roflumilast reportedly improved inflammatory and histopathological changes in asthmatic mice. The current study investigated the effects of oral and rectal roflumilast on trinitrobenzenesulfonic acid (TNBS)-induced chronic colitis in rats, an experimental model resembling human Crohn's disease. Five groups of rats (n=8) were used: normal control, TNBS-induced colitis, and three TNBS-treated colitic groups, which received oral sulfasalazine (500 mg·kg-1·day-1), oral roflumilast (5 mg·kg-1·day-1), or rectal roflumilast (5 mg·kg-1·day-1) for 15 days after colitis induction. Then, the following were assessed: the colitis activity score, tumor necrosis factor (TNF)-α, interleukin (IL)-2, and IL-6 serum levels, colonic length, and myeloperoxidase, malonaldehyde, and glutathione levels. Histological examinations employed H&E, Masson trichrome, and PAS stains in addition to immunostaining for KI-67 and TNF-α. The TNBS-induced colitis rats showed significant increases in disease activity scores, serum TNF-α, IL-2, and IL-6 levels, and colonic myeloperoxidase and malonaldehyde content. They also showed significant decreases in colonic length and glutathione levels in addition to histopathological and immunohistochemical changes. All the treatments significantly improved all these changes. Sulfasalazine provided the greatest improvement, followed by oral roflumilast, and then rectal roflumilast. In conclusion, both oral and rectal roflumilast partially improved TNBS-induced chronic colitis, suggesting the potential of roflumilast as an additional treatment for Crohn's disease.
MeSH term(s)	Aminopyridines/therapeutic use ; Animals ; Benzamides/adverse effects ; Colitis/chemically induced ; Colitis/drug therapy ; Colitis/pathology ; Cyclopropanes ; Disease Models, Animal ; Mice ; Peroxidase ; Rats ; Trinitrobenzenesulfonic Acid/adverse effects ; Tumor Necrosis Factor-alpha
Chemical Substances	Aminopyridines ; Benzamides ; Cyclopropanes ; Tumor Necrosis Factor-alpha ; Roflumilast (0P6C6ZOP5U) ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4) ; Peroxidase (EC 1.11.1.7)
Language	English
Publishing date	2022-02-28
Publishing country	Brazil
Document type	Journal Article
ZDB-ID	786234-9
ISSN	1414-431X ; 0100-879X
ISSN (online)	1414-431X
ISSN	0100-879X
DOI	10.1590/1414-431X2021e11877
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Article ; Online: A novel extended model with versatile shaped failure rate: Statistical inference with Covid -19 applications.

Shafiq, Anum / Sindhu, Tabassum Naz / Alotaibi, Naif

Results in physics

2022 Volume 36, Page(s) 105398

Abstract: Statistical models perform an essential role in data analysis, and statisticians are constantly looking for novel or pretty recent statistical models to fit data sets across a broad variety of fields. In this study, we used modified Kies generalized ... ...

Abstract	Statistical models perform an essential role in data analysis, and statisticians are constantly looking for novel or pretty recent statistical models to fit data sets across a broad variety of fields. In this study, we used modified Kies generalized transformation and the new power function to suggest an unique statistical model. We present and discuss a linear illustration of the density function. Theoretically, quantile function, characteristic function, stochastic ordering, mean, and moments are just a few of the structure properties we discuss. By defining an ideal statistical distribution for assessing the COVID-19 mortality rate, an attempt is performed to determine the model of COVID-19 spread in different nations like the United Kingdom and Italy. In some countries, the novel distribution have been shown to be more appropriate than existing competing models when fitted to COVID-19.
Language	English
Publishing date	2022-03-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2631798-9
ISSN	2211-3797 ; 2211-3797
ISSN (online)	2211-3797
ISSN	2211-3797
DOI	10.1016/j.rinp.2022.105398
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