Fatherhood in disability rehabilitation in the United Arab Emirates: Exploring fathers' involvement in raising children with disabilities.

BACKGROUND: The first agent of socialisation is the family, who are expected to facilitate the inclusion of children in societal activities. While mothers' voices have been widely captured in the literature regarding their experiences raising children with disabilities, fathers' perceptions of their knowledge of and involvement in the development of children with disabilities have been understudied, particularly in non-Western contexts. AIM: The main aim of this study was to examine fathers' perceptions of their involvement in raising children with disabilities in the United Arab Emirates. METHODS AND PROCEDURES: In total, 469 fathers were recruited to understand their involvement in raising their children with disabilities. The Fathers' Involvement in Development and Rehabilitation Scale was used to collect data, which were analysed using SPSS and AMOS. OUTCOMES AND RESULTS: The results showed that fathers rated themselves highly for their attitudes, support, and participation in training to support their children with disabilities. Demographic variables, such as nationality and educational qualifications, provided additional insight into their involvement in raising their children with disabilities. CONCLUSIONS AND IMPLICATIONS: The study concludes with suggestions for training programmes to change fathers' attitudes towards children with disabilities, as such programmes can enable them to better support their children's development.

Endoscopic transcanal coblation excision of glomus tympanicum: a novel technique.

OBJECTIVE: To evaluate the feasibility of coblation in excision of glomus tympanicum tumors. PATIENTS AND METHODS: A retrospective study carried out over 28 patients with types I and II glomus tympanicum tumors according to GLASSCOCK-JACKSON classification. Preoperative radiological and endocrinal evaluation were performed. All patients underwent endoscopic transcanal excision of their glomus tympanicum tumors using coblation. RESULTS: None of the patients developed recurrence during the 1-year follow up period proved radiologically. None of the patients developed facial palsy postoperatively. Differences between preoperative and postoperative dizziness and taste disturbance were statistically non-significant. Tinnitus disappeared completely in 22 patients postoperatively. A statistically significant reduction in Tinnitus Handicap Inventory (THI) after surgery was found. Statistically significant reductions in postoperative air conduction (AC) threshold and air bone gap (ABG) were recorded while bone conduction (BC) threshold showed statistically non-significant change. CONCLUSION: Coblation is an effective and safe tool in excision of glomus tympanicum tumors. Further studies comparing coblation with laser and piezosurgery are strongly recommended.

Superior semicircular canal dehiscence: a radiological and clinical study.

Aim: to assess radiologically the prevalence of SSCD with its clinical presentations and its relationship with age. Methods: a prospective cohort study carried out on 200 consecutive patients (400 temporal bones). Radiological evaluation was performed using High Resolution Computed Tomography (HRCT) with measurement of thickness of bone covering superior semicircular canal (SCC), height and diameter of SSC. Results: Two hundred patients (400 temporal bones) were involved. The mean thickness ± SD, the mean diameter ± SD and the mean height ± SD were 1.38 ± 0.80 mm, 0.94 ± 0.26 mm and 10.91 ± 2.39 mm respectively. The prevalence of SSCD and predehiscence were 1% and 14% respectively. The commonest symptom encountered was autophony (48.3%). When the SSC thickness, diameter and height were compared with the age of patients, statistically significant differences were detected. The highest diameter, lowest height and lowest thickness were found in patients aged from 54 to 72 years. Thickness of bony layer covering SSC was found to be the most validated measurement for differentiation between cases with positive and negative symptoms with the highest sensitivity and specificity. Conclusion: The prevalence of SSCD and predehiscence varied among the studies. Autophony is the commonest symptom usually encountered. The condition is acquired rather than congenital. The thickness of bone covering SCC is the most validated measurement in differentiation between cases with positive and negative symptoms.

Predictors of effusion viscosity in otitis media with effusion: neutrophil lymphocyte ratio versus mean platelet volume.

OBJETIVOS: comparar entre el índice de neutrófilos linfocitos (NLR) y el volumen plaquetario medio (VPM) en la predicción de la viscosidad del derrame en la otitis media con derrame. MATERIALES Y MéTODOS: Se incluyeron en el estudio 248 niños con derrame en el oído medio. Se evaluaron los hemogramas completos (CBC) preoperatorios. Se registraron los valores de NLR y MPV. La viscosidad del derrame se evaluó durante la cirugía mientras se aspiraba el derrame después de la miringotomía. Se clasificaron 2 tipos de derrames; tipos serosos y mucoides. RESULTADOS: se reportaron diferencias estadísticamente significativas en NLR y MPV entre los derrames serosos y mucoides. Los valores de corte de NLR y MPV para diferenciar entre derrames serosos y mucoides fueron 1,21 y 7,95 respectivamente. Cuando se compararon NLR y MPV, NLR pareció tener mayor sensibilidad, especificidad y precisión diagnóstica que MPV. CONCLUSIóN: NLR es superior a MPV como predictor de la viscosidad del derrame en otitis media con derrame. Ambos marcadores se consideran rentables y fiables para la evaluación de la viscosidad del derrame.

Endoscopic ossiculoplasty in traumatic conductive hearing loss with intact tympanic membrane: a five-year experience.

BACKGROUND: Exploratory tympanotomy in cases of traumatic ossicular disruption with intact tympanic membrane is crucial for both diagnostic and therapeutic purposes. Performing this procedure using the endoscope is gaining popularity. Hence, this study aimed to demonstrate varieties of ossicular pathology and their management in our institution. METHODS: A retrospective evaluation was conducted of 136 ears in patients with traumatic ossicular disruption with an intact tympanic membrane, who underwent endoscopic exploratory tympanotomy. A proposed algorithm was followed, to incorporate different traumatic ossicular possibilities. Assessment of hearing outcomes and surgical complications was performed six months post-operatively. RESULTS: Incudostapedial dislocation was the most commonly encountered type of traumatic ossicular disruption (35.3 per cent). Air conduction threshold improved significantly following endoscopic ossiculoplasty, from 50.9 ± 6.35 dB pre-operatively to 22.35 ± 3.27 dB post-operatively, with successful air-bone gap closure. CONCLUSION: Endoscopic ear surgery is effective in the diagnosis and management of challenging cases of post-traumatic ossicular disruption with an intact tympanic membrane.

Spectrum subtraction as a complementary method for six resolution techniques resolving overlapping spectra; application to multicomponent veterinary formulation with greenness and whiteness assessment.

Mathematical filtration is an efficient tool to resolve the overlapping spectra of binary mixtures in zero or first order form. Herein, a comparative study was conducted between six economic, accurate and precise spectrophotometric methods for determination of Triclabendazole (TCB) and Levamisole HCl (LVM). Each component was resolved with minimum mathematical steps in its zero-order absorption spectrum by ratio subtraction, constant multiplication, and the recent factorized response method; coupled with spectrum subtraction. In addition, the mixture was resolved in its first derivative form by derivative subtraction, D1 constant multiplication, and the recent D1 factorized response method; coupled with spectrum subtraction. Results obtained were also compared to those obtained from constant value, concentration value, and derivative ratio methods. The linearity range was found to be either 1.0-10.0 µg/mL or 2.0-20.0 µg/mL for TCB, and 2.0-14.0 µg/mL for LVM with LOD of 0.08 µg/mL and 0.19 µg/mL, respectively. Validation of the proposed methods was performed according to VICH guidelines. Results obtained from the statistical data showed no significant difference regarding accuracy and precision compared to the reported methods. The developed spectrophotometric methods followed the principles of green analytical chemistry, in which the green assessment was done through four tools, called, National Environmental Methods Index (NEMI), Analytical Eco-Scale (AES), Green Analytical Procedure Index (GAPI) and Analytical greenness metric (AGREE). Also, a white assessment was performed using RGB model. The proposed methods could offer an economic alternative for the routine analysis of bulk materials and combined veterinary dosage form.

Novel eco-friendly spectrophotometric approaches for resolution of fixed dose formulation of phenylbutazone with minor component of dexamethasone: Greenness assessment by AGREE tool.

Spectrophotometric resolution of severely overlapped binary mixtures with minor component is challenging. Herein, coupling of mathematical manipulation steps with sample enrichment was conducted on the binary mixture spectrum of Phenylbutazone (PBZ) and Dexamethasone sodium phosphate (DEX) to resolve, for the first time each component separately. Simultaneous determination of both components in a mixture ratio of 1:0.002 was achieved in their zero or first order spectra by the recent factorized response method along with ratio subtraction and constant multiplication methods; all coupled with spectrum subtraction. In addition, a novel second derivative concentration value and second derivative constant value methods were developed for PBZ determination. The concentration of the minor component DEX was obtained, without preliminary separation steps by derivative ratio after sample enrichment by either spectrum addition or standard addition. Spectrum addition approach showed superior characteristics compared to standard addition technique. All proposed methods were placed through a comparative study. Linear correlation was found to be 1.5-18.0 µg/mL for PBZ, and 4.0-45.0 µg/mL for DEX. The proposed methods were validated in accordance with ICH guidelines. The greenness assessment of the proposed spectrophotometric methods was evaluated by AGREE software. Results obtained from the statistical data were evaluated by comparing to one another as well as the official USP methods. These methods offer a cost and time effective platform to analyze bulk materials and combined veterinary formulation.

A Novel, Sustainable, and Eco-Friendly Spectrophotometric and Chemometric Approach for Determination of Severely Overlapped Spectrum via Unified Regression Equation: Greenness and Whiteness Assessment.

BACKGROUND: Nebivolol and valsartan (VAL) in combination with each other successfully control blood pressure and improve hypertension patient outcomes. OBJECTIVE: To develop and validate innovative, simple, and sustainable spectrophotometric methods for the simultaneous analysis of nebivolol and valsartan. METHOD: The new modified difference amplitude modulation (MD-AM) method uses only unified regression equation and does not require any resolution techniques. Other different approaches were also applied for the determination of the same mixture including univariate and multivariate spectrophotometric methods. The multivariate methods were PLS and PCR, whereas the univariate methods were derivative ratio (DD1), ratio difference (RD), constant center (CC), constant center spectrum subtraction (CC-SS), constant value coupled with amplitude difference (CV-AD), advanced concentration value (ACV), and amplitude difference (AD). The proposed methods use a green solvent; thus, the environmental impact of the presented procedures was evaluated qualitatively and quantitatively using six well-known evaluation tools. RESULTS: All methods were applied successfully for the analysis of the studied drugs in their bulk powder, pharmaceutical dosage form Byvalson®, and in vitro release at intestinal pH (7.4) using a USP dissolution tester. Results obtained were compared statistically with the reported method and with each other using a one-way ANOVA statistical test, and no significant differences were found. CONCLUSIONS: All green and white analytical chemistry evaluation tools results confirm the safety, sustainability, and cost-effectiveness of the approaches, indicating that the methods are regarded green and sustainable. Results were agreeable, encouraging their applicability in quality control laboratories for dosage form and making these methods an eco-friendly substitute for the analysis of this combined dosage form and for evaluating the dissolution profile. HIGHLIGHTS: For the first time, a severely overlapped spectrum was determined using a unified regression equation without the need of extended part or zero contribution regions by the novel method MD-AM. The proposed methods are the first study of in vitro dissolution profiling of nebivolol hydrochloride (NEB) and VAL and the first sustainable and green methods applied without compromising the analytical criteria.

Endoscopic stapedotomy: classic versus reversal technique.

OBJECTIVES: To compare hearing outcome and surgical complications between endoscopic classic and reversal stapedotomies. PATIENTS AND METHODS: A prospective single blinded randomized clinical study carried out on 60 patients with otosclerosis who were randomized into two groups; each containing 30 patients. Patients in group 1 underwent endoscopic classic stapedotomy. Patients in group 2 underwent endoscopic reversal stapedotomy. Both groups were compared as regards hearing outcome and surgical complications. RESULTS: The difference in the hearing outcome between the two groups was statistically non-significant. Post-operative closure of the air bone gap (ABG) within 10 dB was attained in 76.67% and 80% of patients in groups 1 and 2, respectively. The differences in the surgical complications between the two studied groups were statistically non-significant. CONCLUSION: Endoscopic classic and reversal stapedotomies are comparable to each other as regards hearing outcome and surgical complications. The authors recommend further studies with relatively larger sample size.

Endoscopic transcanal management of incus long process defects: rebridging with bone cement versus incus interposition.

OBJECTIVES: to compare hearing outcomes between endoscopic transcanal rebridging with bone cement and endoscopic transcanal incus interposition in patients with incus long process defects secondary to chronic suppurative otitis media (inactive mucosal type). METHODS: This retrospective study was performed on 83 ears of 83 consecutive patients with incus long process defects secondary to chronic suppurative otitis media (inactive mucosal type). According to the extent of incus long process erosion and subsequent ossiculoplasty technique, patients were divided into 2 groups. Patients in group 1 had erosion involving up to two thirds of the length of the incus long process and underwent endoscopic transcanal rebridging with bone cement. Patients in group 2 had erosion involving more than two thirds of the length of the incus long process and underwent endoscopic transcanal incus interposition. RESULTS: Hearing gain (mean ± standard deviation) was 21.39 ± 2.15 dB in group 1 and 19.71 ± 6.12 dB in group 2. A significantly greater hearing gain was achieved in bone cement group than in incus interposition group (P value < 0.001). Successful hearing outcome (post-operative air bone gap closure within 20 dB) was achieved in 81.6% and 71.1% of patients of group 1 and group 2 respectively. CONCLUSION: Endoscopic transcanal rebridging with bone cement offers greater hearing gain than endoscopic transcanal incus interposition. The two techniques remain reliable and cost-effective techniques in management of patients with incus long process defects. The main limitation of this study was the short follow-up period. Further studies with relatively long-term follow-up are strongly recommended.

In Vitro Dissolution Profile of Antihypertensive Mixture: Comparison Between Multivariate Methods and Statistical and Graphical Representation of Different Univariate Spectrophotometric Data.

BACKGROUND: Triplixam® is a new antihypertensive drug combination consisting of perindopril, amlodipine, and indapamide, which have a synergistic mechanism of action in combination with each other. OBJECTIVE: Comparative study of different spectrophotometric approaches used for the simultaneous determination of perindopril, indapamide, and amlodipine in bulk powder and in dosage form Triplixam. METHOD: The methods include univariate and multivariate spectrophotometric methods depending on either mathematical calculation or graphical representation of data. For the univariate methods: perindopril was resolved from other components using constant multiplication followed by spectrum subtraction resolution technique, and then two base point, AUC, constant value, and concentration value (CNV) methods were applied. For both amlodipine and indapamide: constant multiplication resolution technique was used, and then constant value and CNV methods were applied. CNV depends on graphical representation of data rather than statistical data. PLS and PCR chemometric assisted spectrophotometric techniques were also applied. The proposed methods are considered a green alternative to the reported methods as the greenness of the proposed methods was evaluated qualitatively and quantitatively by four green analytical evaluation tools. RESULTS: The methods were applied for the analysis of the mixture in the pharmaceutical dosage form Triplixam and in vitro release at intestinal pH (7.4) using a USP dissolution tester. CONCLUSIONS: The proposed green analytical methods are considered to be greener than the reported methods and simpler, so they could be used as an alternative for routine analysis of the mixture in quality control laboratories for the reason of their accurate results beside minimum manipulation steps that reduced the error and time required of the analysis with no harmful effect on analyst health as well as the environment. HIGHLIGHTS: The study was the first in vitro dissolution profiling of perindopril, amlodipine, and indapamide. The developed methods were excellent green methods without compromising the analytical criteria.

A refashioned foley catheter: novel cost-effective available stent in pediatric laryngotracheal reconstruction.

PURPOSE: Pediatric laryngotracheal reconstruction (LTR) for laryngotracheal stenosis (LTS) mandates stenting in certain situations. This study presents a novel commercially available and cost-effective stent, a refashioned foley catheter. METHODS: This prospective clinical study was performed on pediatric cases with LTS up to 8 years. The study was performed in a tertiary referral center. The selection of the proper foley catheter size for age was explained. The atraumatic insertion maneuver of the stent was also shown in detail in different situations of LTS. The endoscopic removal of the stent was also described. The mean follow-up was 6.45 ± 1.3 months. RESULTS: The study included 31 cases using the refashioned foley catheter stents. The study included 17 males and 14 females with a mean age of 3.45 ± 1.09. Subglottic stenosis was the most common cause of LTR in the study (74.2%) cases. The mean duration of stenting was 40.5 ± 3.7 days. Decannulation was achieved in 96.8% of cases. No stent complications were encountered like stent migration, excess granulation tissue, intractable aspiration, or pressure necrosis. CONCLUSION: The refashioned foley catheter is a novel, available, and inexpensive stent that can be utilized for LTR cases for pediatric LTS. The newly described stent is soft, pliable with atraumatic insertion and easy endoscopic removal with minimal complications.

Kinetic degradation study for the first licensed anti-influenza polymerase inhibitor, baloxavir marboxil, using high-performance liquid chromatography-mass spectrometry.

The first licensed polymerase inhibitor, baloxavir marboxil was recently approved for the treatment of influenza A and B viruses. Furthermore, there is growing interest in testing the antiviral activity of baloxavir marboxil against Coronavirus. Despite its critical clinical value, there is no information on the degradation products, pathways, or kinetics of baloxavir marboxil under various stress conditions. In this study, a new high-performance liquid chromatography-ultraviolet detection method for accurately quantifying baloxavir marboxil in the presence of its degradation products was developed. A study of degradation kinetics revealed that acidic, thermal neutral, and photolytic degradation reactions have zero-order kinetics, whereas basic and oxidative degradation reactions have first-order kinetics. The structural characterization of baloxavir marboxil degradation products was performed by coupling the optimized high-performance liquid chromatography method to the triple-quadrupole tandem mass spectrometer. The proposed approach was validated according to the International Council for Harmonisation Q2 (R1) requirements for accuracy, precision, robustness, specificity, and linearity. The validated new method was successfully used to analyze baloxavir marboxil as raw material and its pharmaceutical dosage form, Xofluza.

Development and Validation of Stability-Indicating Assay Method for a Novel Oxazolidinone (PH-192) with Anticonvulsant Activity by Using UHPLC-QToF-MS.

The treatment of seizure disorders with currently available pharmacotherapeutic agents is not optimal due to the failure of some patients to respond, coupled with occurrences of side effects. There is therefore a need for research into the development of new chemical entities as potential anticonvulsant agents, which are different structurally from the existing class of drugs. We recently identified a novel triazolyl-oxazolidinone derivative, PH-192, as a potential anticonvulsant agent. PH-192 demonstrated protection comparable to phenytoin against both chemically- and electrically-induced seizures in rodents with little or no central nervous system side effects. However, PH-192 did not exhibit protection beyond 30 min; therefore, we decide to investigate a stability-indicating assay of PH-192 in plasma and other solutions. A reliable and validated analytical method was developed to investigate the stability of PH-192 for 90 min in human plasma, acidic, basic, and oxidative conditions, using a Waters Acquity ultra high-performance liquid chromatography (UHPLC) system with a quaternary Solvent Manager (H-Class). A simple extraction method indicated that PH-192 was stable in human plasma after 90 min at 37 °C, with more than 90% successfully recovered. Moreover, stress stability studies were performed, and degradants were identified using LC-QToF-MS under acidic, basic, and oxidative simulated conditions.

Endoscopic transcanal attico-antrostomy versus endoscopic-assisted canal wall up mastoidectomy in management of localized cholesteatoma: a randomized clinical trial.

OBJECTIVES: This study aims to compare results of endoscopic transcanal tympanoplasty with attico-antrostomy with endoscopic-assisted canal wall up mastoidectomy in treatment of cases of limited attic cholesteatoma. MATERIALS AND METHODS: A prospective randomized single-blinded study involving 40 patients with limited attic cholesteatoma was conducted. Randomization of the patients into two groups was done; 20 patients are managed by endoscopic transcanal tympanoplasty with attico-antrostomy, while the other 20 patients are managed by endoscopic-assisted canal wall up mastoidectomy. Primary outcome is recidivism, while secondary outcomes include hearing results, operative time, pain score and associated complications. RESULTS: Comparable recidivism rate was found in the two groups. The endoscopic-assisted canal wall up mastoidectomy group was associated with significantly longer duration of surgery and higher postoperative pain score. There was no significant difference between both the groups regarding hearing results and associated complications. CONCLUSION: In localized attic cholesteatoma cases, endoscopic transcanal tympanoplasty with attico-antrostomy is a time-saving less-invasive reliable technique with good eradication results. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov (NCT04959539) "retrospectively registered" at 12/7/2021.

Nutritional predictors of pharyngocutaneous fistula after total laryngectomy: A multivariate analytic study in a single institution.

OBJECTIVE: The objective of this study was to evaluate, through multivariate analysis, the configuration of nutritional predictors that impact the development pharyngocutaneous fistula (PCF) after total laryngectomy. METHODS: A retrospective cohort study carried out on 203 consecutive patients with laryngeal squamous cell carcinoma who underwent total laryngectomy with neck dissection between June 2015 and June 2020. Patients with risk factors for PCF formation, other than malnutrition, were excluded to eliminate the potential impact of that risk factors on PCF formation and to make the study group homogenous. Five parameters were evaluated including preoperative serum prealbumin, albumin and transferrin levels, Body Mass Index (BMI) and Malnutrition Screening Tool (MST). RESULTS: Univariate analysis revealed that preoperative prealbumin, albumin and transferrin levels significantly correlated with PCF development. Multivariate logistic regression analysis revealed that preoperative prealbumin level was the best independent nutritional predictor of PCF (P value <0.001, odd ratio 11.951 [95% CI 3.686-38.749]) followed by preoperative albumin (P value 0.006, odd ratio 3.985 [95% CI 1.485- 10.694]). CONCLUSION: Preoperative prealbumin level is considered the best independent nutritional predictor of PCF. It should be used to evaluate the nutritional status of patients undergoing total laryngectomy and hence their need for nutritional support.

Mathematical Modeling for HPLC Separation and Quantification of an Anti hypertensive Combination by Response Surface Methodology.

BACKGROUND: Determination of a multi-component mixture by HPLC requires many preliminary runs for method development which is both time-consuming and expensive due to the usage of large solvent volumes. OBJECTIVE: In the present study, the main objective was to reduce the preliminary runs that are required for optimizing the method conditions and also shorten the run time of analysis to be suitable for quality control laboratories where there are a large number of samples to be analyzed. METHODS: That was achieved using a two-factor, three-level response surface experiment which is a multivariate design that predicts the significant factors for optimizing the studied responses. RESULTS: The response surface design suggests that both acetonitrile ratio and flow rate are significant factors for full resolution of the studied mixture: atenolol, amiloride, and hydrochlorothiazide. The studied mixture was fully separated and determined in less than 5 min with perfect resolution. CONCLUSION: Experimental design is a very beneficial tool for optimization of the method conditions in HPLC, especially if the studied mixture ingredients have overlapping peaks. For atenolol, amiloride, and hydrochlorothiazide, acetonitrile and flow rate were found to be the significant factors that affected the resolution of the studied mixture. HIGHLIGHTS: Response surface design is a powerful tool that could be used for predicting the significant factors for separation in HPLC. Optimization of the method conditions was done using a limited number of preliminary runs. The studied ternary mixture was fully separated in less than 5 min with the aid of experimental design.

Development of a multivariate model with desirability-based optimization for determination of atenolol and hydrochlorothiazide by eco-friendly HPLC method with fluorescence detection.

Determination of a widely used antihypertensive combination of atenolol and hydrochlorothiazide was achieved by rapid and eco-friendly high-performance liquid chromatography method combined with fluorescence detection. The response surface methodology is conducive to the complete separation of the two drugs in a shorter analysis time. The separation of the mixture was achieved using an Inertsil C18 analytical column (150 × 4.6 mm, 5 µ). The mobile phase used was ethanol: potassium dihydrogen phosphate at pH 3 (65:35 v/v) and the flow rate was 0.7 mL/min. The fluorescence detector operated at excitation and emission wavelengths of 230 and 310 nm (atenolol) and 270 and 375 nm (hydrochlorothiazide). The linearity of the developed method covered a concentration of atenolol of 0.05-5 µg/mL and a concentration of hydrochlorothiazide of 0.02-1 µg/mL. The greenness of the developed method was evaluated by analytical eco-scale and the recently reported evaluation method, that is, green analytical procedure index, and it was found to be an excellent, sensitive, and green alternative to the reported methods. The developed method was validated according to the ICH guidelines and compared with the reference method. No significant difference was found in terms of accuracy.

Modulation of rifampicin-induced hepatotoxicity using poly(lactic-co-glycolic acid) nanoparticles: a study on rat and cell culture models.

Aim: Hepatotoxicity is the most serious adverse effect of rifampicin (RIF). We aimed to investigate the potential hepatoprotective effect of mannose-functionalized poly(lactic-co-glycolic acid)(PLGA)/RIF nanoparticles (NPs) in rats as a possible promising approach to minimize RIF-induced hepatotoxicity. Materials & methods: Mannose-functionalized PLGA/RIF NPs were fabricated and characterized in vitro, then the hepatoprotective effect of optimized NPs was studied on rat and cell culture models. Results: Following intraperitoneal administration of RIF NPs into rats, highly significant differences in levels of serum transaminases and oxidative stress markers, associated with significant differences in expression of Bax and Bcl-2 genes between NP- and free RIF-treated groups, revealing the hepatoprotective potential of NPs. Conclusion: RIF NPs may represent a promising therapeutic approach for tuberculosis via reducing dose frequency and consequently, RIF-induced hepatotoxicity.

Development of a Robust UPLC Method for Simultaneous Determination of a Novel Combination of Sofosbuvir and Daclatasvir in Human Plasma: Clinical Application to Therapeutic Drug Monitoring.

A rapid and selective UPLC-DAD method was developed and validated for simultaneous analysis of the novel two-drug combination Darvoni® for the treatment of HCV: Sofosbuvir (SF)/Daclatasvir (DC) in human plasma using Ledipasvir as internal standard (IS) where the extraction process was conducted using automated SPE. Although the analysis of the combination after concomitant oral intake of two tablets of SF and DC individually was reported in literature, yet simultaneous analysis of this new combination in human plasma after a single oral dose was not previously reported. The adopted chromatographic separation was achieved on Waters® Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) as a stationary phase using isocratic elution using a mobile phase system of ammonium formate (pH 3.5; 5 mM) and acetonitrile (60:40 v/v) pumped at a flow rate of 0.2 mL.min-1. The UV detection was carried out at 261 nm for SF and 318 nm for DC and IS. SF was eluted at 1.123 min while DC was eluted at 3.179 min. The proposed chromatographic method was validated in accordance with guidelines of FDA for bioanalytical method validation. A linear range was achieved in the range of 25-6400 and 50-12800 ng.mL-1 for SF and DC, respectively. The proposed UPLC-DAD method was found to be accurate with % bias ranging between -10.0-7.2 for SF and -6.9-8.0 for DC. Also it was proved to be precise with % CV for intraday precision ranging between 3.8-9.6 for SF and 2.8-9.2 for DC whereas interday precision ranged between 5.1-9.3 for SF and 3.7-9.1 for DC. Moreover, % extraction recovery ranged between 90.0-107.2 for SF and 93.1-108.0 for DC using the suggested method. The adopted chromatographic method was successfully applied to the therapeutic drug monitoring of SF and DC in healthy volunteers after the oral intake of one Darvoni® tablet.