Exploring the Feasibility of a Bracketing Approach Utilizing Modeling for Development of Long-Acting Injectables for Regulatory Approval-A Case Study Using Levonorgestrel.

Background: The development of long-acting products of a characterized drug substance is of great interest. It is possible to support the development of these products with available clinical data by matching the exposure to a predefined bracket of a minimal concentration for efficacy and a maximal concentration for safety. This bracketing approach would cut down on the time and cost of new long-acting contraceptive products progressing to market.

Retention in care among people living with human immunodeficiency virus (HIV) in a low-resource setting.

Background: This study aimed to evaluate the retention in care among a cohort of Egyptian people living with HIV (PLWHIV).

Method: The study was conducted on PLWHIV attending Kasr Alainy HIV and Viral Hepatitis Centre, Cairo, Egypt, from January 1, 2019, to March 31, 2023. PLWHIV were considered not retained in care if there was no documented clinical visit or HIV viral load (VL) or CD4 count test for more than 6 months from their last recorded visit or test.

Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.

Background: Ulcerative colitis (UC) is an idiopathic chronic inflammation of colonic and rectal mucosa. The peroxisome proliferator-activated receptor α (PPARα) has been identified as having protective effects in UC.

Aim: The study aimed to investigate the efficacy of fenofibrate, a PPARα agonist, in UC.

A randomized controlled trial comparing tacrolimus versus hydrocortisone for the treatment of atopic dermatitis in children: new perspectives on interferon gamma-induced protein and growth-related oncogene-α.

Introduction: Atopic dermatitis (AD) is a type of chronic inflammatory disorder that affects children.

Aim: To investigate whether hydrocortisone or tacrolimus could be more effective for treating AD in children.

Patients And Methods: This clinical randomized investigation included 100 children with AD who met the eligibility criteria.

A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.

The Simcyp Simulator is a software platform widely used in the pharmaceutical industry to conduct stochastic physiologically-based pharmacokinetic (PBPK) modeling. This approach has the advantage of combining routinely generated in vitro data on drugs and drug products with knowledge of biology and physiology parameters to predict a priori potential pharmacokinetic changes in absorption, distribution, metabolism, and excretion for populations of interest. Combining such information with pharmacodynamic knowledge of drugs enables planning for potential dosage adjustment when clinical studies are feasible.

Correlation between depression scores and serum NF-ĸB/NLRP3 axis, biotinidase, and HMGB1 after treatment with isotretinoin in patients with acne vulgaris.

Background: Acne vulgaris (AV) is an inflammatory skin disorder leading to scars and discomfort, its intensity has major psychological consequences such as depression.

Aim: To investigate the effect of isotretinoin (ISO) on NF-κB/NLRP3, biotinidase, and HMGB and correlation with depression.

Patients And Methods: This was a case-control study that involved two groups.

Hyaluronidase impacts exposures of long-acting injectable paliperidone palmitate in rodent models.

A significant challenge in the development of long-acting injectable drug formulations, especially for anti-infective agents, is delivering an efficacious dose within a tolerable injection volume. Co-administration of the extracellular matrix-degrading enzyme hyaluronidase can increase maximum tolerable injection volumes but is untested for this benefit with long-acting injectable formulations. One concern is that hyaluronidase could potentially alter the tissue response surrounding an injection depot, a response known to be important for drug release kinetics of long-acting injectable formulations.

The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19.

Objective: Type 2 diabetes mellitus (T2DM) is regarded as a chief risk factor for(coronavirus disease 2019 (COVID-19) owing to dysregulation of the expression of angiotensin-converting enzyme 2 (ACE2) and chronic low-grade inflammatory disorders. Metformin, an insulin-sensitizing agent for managing T2DM, has pleiotropic anti-inflammatory and oxidant potentials, which may lessen the risk of diabetic complications. So, we aimed to reveal the potential role of metformin monotherapy in treating T2DM patients with COVID-19.

Complementarity of two proteomic data analysis tools in the identification of drug-metabolising enzymes and transporters in human liver.

Several software packages are available for the analysis of proteomic LC-MS/MS data, including commercial ( Mascot/Progenesis LC-MS) and open access software ( MaxQuant). In this study, Progenesis and MaxQuant were used to analyse the same data set from human liver microsomes ( = 23). Comparison focussed on the total number of peptides and proteins identified by the two packages.

A randomized placebo-controlled, double-blind study to investigate the effect of a high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients, new insights on serum STAT-3 and hepassocin.

Objective: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver metabolic disease affecting millions globally. This study aimed to assess the safety and efficacy of a high oral loading dose of cholecalciferol supplement on NAFLD patients and to investigate its potential role on serum inflammatory biomarkers.

Patients And Methods: One hundred patients with NAFLD and type 2 diabetes mellitus were involved in the study.

Genetic polymorphisms effect on cyclophosphamide's tolerability and clinical efficacy in Egyptian patients with lupus nephritis.

Objectives: Many studies were conducted to determine the association between genetic polymorphisms in CYP2B6 c.516G>T and cyclophosphamide (CYC) efficacy or toxicity, no studies were focused on both clinical efficacy and toxicity of CYC. This study aimed to investigate the relationship between the CYP2B6 c.

Interplay between the Brassica napus phytoglobin (BnPgb1), folic acid, and antioxidant responses enhances plant tolerance to waterlogging.

Oxygen deprivation by waterlogging reduces the productivity of several crop species, including the oil-producing crop Brassica napus L., which is highly sensitive to excess moisture. Among factors induced by oxygen deficiency are phytoglobins (Pgbs), heme-containing proteins known to ameliorate the response of plants to the stress.

Using Prior Knowledge on Systems Through PBPK to Gain Further Insight into Routine Clinical Data on Trough Concentrations: The Case of Tacrolimus in Chronic Kidney Disease.

Background: Routine therapeutic drug monitoring (TDM) relies heavily on measuring trough drug concentrations. Trough concentrations are affected not only by drug bioavailability and clearance, but also by various patient and disease factors and the volume of distribution. This often makes interpreting differences in drug exposure from trough data challenging.

Metabolic Analysis of Methylenetetrahydrofolate Reductase Single Nucleotide Polymorphisms (MTHFR 677C

Neural tube defects (NTDs) are among the most prevalent and debilitating birth defects with their causes are still unknown, despite mounting evidence that genetic and/or environmental factors may play a role. We aimed to analyze two single nucleotide polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene, serum folate and vitamin B12 status among a cohort of Egyptian children with NTDs and their mothers. A case-control study has been conducted on 50 Egyptian children with various types of NTDs and their mothers.

Evaluation of needling-induced autoinoculation in the management of genital warts.

Background: Genital warts caused by human papillomavirus (HPV) are one of the most common sexually transmitted infections. Long latency, lesions' multiplicity, high recurrence rate, and the tendency to malignant transformation are essential challenges during management. Traditional treatment modalities are known to be lesion-directed while intralesional immunotherapy was introduced to act beyond individual lesions and to confront the previous challenges through injection of known antigens, such as measles, mumps and rubella (MMR) vaccine, to stimulate the immune system against HPV.

Evaluating the safety and efficacy of the leukotriene receptor antagonist montelukast as adjuvant therapy in obese patients with type 2 diabetes mellitus: A double-blind, randomized, placebo-controlled trial.

Type 2 diabetes mellitus (T2DM) is common with obesity. Metformin is a first-line therapy for this condition. However, it has only a minor impact on weight loss in some patients.

Outcome of Long-Segment Fixation versus Inclusion of the Fractured Level in Short-Segment Fixation for Thoracolumbar Junction Fractures.

 The aim of this study was to compare the radiological outcomes of long-segment fixation and short-segment fixation, including the fracture level in patients treated for thoracolumbar junction fractures.  Data collected from records of patients with thoracolumbar junction fractures who were operated at our department. Neurological evaluation was done using American Spinal Injury Association classification score.

Serial changes in renal indices in chronic HCV patients with and without HIV co-infection receiving sofosbuvir and tenofovir-based therapies.

Background: Sofosbuvir (SOF) is authorized for hepatitis C virus (HCV) patients. The nephrotoxicity of SOF on HCV mono-infected and HCV-human immunodeficiency virus (HIV) individuals receiving antiretroviral therapy (ART) remains controversial.

Methods: A prospective study including 159 HCV mono-infected and 124 HCV-HIV individuals (47 were ART naïve and 77 were tenofovir [TDF]-based ART) who presented with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.

Randomized Clinical and Biochemical Study Comparing the Effect of L-arginine and Sildenafil in Beta Thalassemia Major Children With High Tricuspid Regurgitant Jet Velocity.

Background: Pulmonary hypertension (PHT) is common in β-thalassemia patients due to hemolysis, iron overload and diminished nitric oxide (NO) levels. Biochemical markers can help to understand the pathophysiology and to introduce new therapies for this condition.

Aim: This study aimed to evaluate the effectiveness of L-arginine and sildenafil in thalassemia children with PHT at both clinical and biochemical levels.

Lab-scale production of anti-Schistosoma monoclonal antibodies by hybridoma culturing in serum free medium: Enhancement of growth, cryopreservation survival rate, and diagnostic accuracy.

This study was performed to evaluate the effect of two commercially available serum-free culture media; serum free medium (SFM) and chemically defined medium (CDM), on the growth rate, antibody productivity and post adaptation cryopreservation and revival reactivity of hybridoma cells compared to the conventional serum based medium (SBM). In addition, the diagnostic efficacy of MAbs secreted in each culture medium was evaluated by testing their performance in sandwich ELISA for antigen detection. Anti- Schistosoma mansoni soluble egg antigen hybridoma cell line (7A/8F) secreting previously characterized IgG Kappa mAbs, were retrieved and propagated in each of the three aforementioned media.

Circulating Ubiquitin Carboxyl Terminal Hydrolase L1 and Neuroglobin Levels in Traumatic Spinal Cord Injuries: Relation to Severity and Outcomes.

Introduction: Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI.

Methods: This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers.

Proteomic quantification of perturbation to pharmacokinetic target proteins in liver disease.

Model-based assessment of drug pharmacokinetics in liver disease requires quantification of abundance and disease-related changes in hepatic enzymes and transporters. This study aimed to assess performance of three label-free methods [high N (HiN), intensity-based absolute quantification (iBAQ) and total protein approach (TPA)] against QconCAT-based targeted data in healthy and diseased (cancer and cirrhosis) liver tissue. Measurements were compared across methods and disease-to-control ratios provided a 'disease perturbation factor' (DPF) for each protein.

Rotation Advancement Keystone Flap for Closure of Large Myelomeningocele Defects.

Introduction: Myelomeningocele is the most common form of neural tube anomalies. Early reliable skin coverage should be achieved to reduce central nervous system infections. The keystone flaps are gaining popularity for myelomeningocele defect reconstruction.

A family of QconCATs (Quantification conCATemers) for the quantification of human pharmacological target proteins.

We have developed a family of QconCAT standards for the absolute quantification of pharmacological target proteins in a variety of human tissues. The QconCATs consist of concatenated proteotypic peptides, are designed in silico, and expressed in E. coli in media enriched with [C] arginine and [C] lysine to generate stable isotope-labeled multiplexed absolute quantification standards.