P-doped carbon dot nano-probe for inner filter effect-based determination of sarecycline in pharmaceutical dosage form and human plasma.

Based on novel phosphorus-doped carbon dots (PCDs), a simple, quick, and accurate fluorescence probe for sarecycline (SAR) determination has been created. The PCDs were prepared in just five minutes using green, straightforward one-step microwave pyrolysis. To create the PCD probe, sodium phosphate monobasic was utilized as a phosphorus dopant and citric acid as a carbon supply. The proposed synthesis method was energy efficient and yielded CDs with a narrow particle size distribution. Based on inner-filter effect mechanism, the generated PCDs were used as nano-probe for SAR determination. The fluorescence quenching intensity showed a strong linear relationship with SAR concentration in the 3-90-µM range with a detection limit of 0.88 µM. Because there is no surface alteration of the CDs or creation of a covalent bond between SAR and PCDs, the developed approach is quick, easy, inexpensive, and requires less time. The new probe's enhanced sensitivity, broad linear range, and acceptable selectivity made it suitable for SAR measurement in pharmaceutical formulations and spiked human plasma. Most importantly, the Green Analytical Procedure Index (GAPI) and Analytical GREEnness (AGREE) assessments showed that the suggested method was environmentally friendly.

Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?

Tyrosine kinase inhibitors (TKIs) represent a relatively large class of small-molecule inhibitors that compete with ATP for the catalytic binding site of tyrosine kinase proteins. While TKIs have demonstrated effectiveness in the treatment of multiple malignancies, including chronic myelogenous leukemia, gastrointestinal tumors, non-small cell lung cancers, and HER2-overexpressing breast cancers, as is almost always the case with anti-neoplastic agents, the development of resistance often imposes a limit on drug efficacy. One common survival response utilized by tumor cells to ensure their survival in response to different stressors, including anti-neoplastic drugs, is that of autophagy. The autophagic machinery in response to TKIs in multiple tumor models has largely been shown to be cytoprotective in nature, although there are a number of cases where autophagy has demonstrated a cytotoxic function. In this review, we provide an overview of the literature examining the role that autophagy plays in response to TKIs in different preclinical tumor model systems in an effort to determine whether autophagy suppression or modulation could be an effective adjuvant strategy to increase efficiency and/or overcome resistance to TKIs.

LncRNA ILF3AS1, MMP3, and MMP9 as well as miRNA-212 as emerging novel biomarkers for childhood epilepsy.

Background: Globally, approximately 70 million people suffer from epilepsy. Infants constitute a significant percentage of these cases. Hence, there is a significant need for better understanding of the pathophysiology of epilepsy through laboratory and radiological methods for early detection and optimized management. Interleukin enhancer binding factor 3 antisense RNA l (ILF3AS1) is a long non-coding RNA (lncRNA) that enhances the expressions of matrix metalloproteinase 3 (MMP3) and matrix metalloproteinase 9 (MMP9), which are considered to be epileptogenic. Aim: We aimed to assess the serum expressions of the lncRNAs ILF3AS1, MMP3, and MMP9 along with microRNA-212 (miRNA-212) as predictive biomarkers in children with epilepsy; we also assessed their correlations with magnetic resonance imaging (MRI) findings. Subjects and Methods: Fifty children with epilepsy and fifty healthy controls were considered in this study. Serum expressions of the lncRNA ILF3AS1 and miRNA-212 were estimated by quantitative real-time polymerase chain reaction (qPCR). Serum concentrations of MMP3 and MMP9 were estimated by enzyme-linked immunosorbent assay (ELISA) in parallel with MRI findings and different baseline biochemical parameters of all the subjects. Results: The results showed significantly higher levels of lncRNAs ILF3AS1, MMP3, and MMP9 as well as lower levels of miRNA-212 in children with epilepsy compared to the controls. The fold-change of miRNA-212 was a significant negative predictor (odds ratio = 0.153, p = 0.000). The receiver operating characteristic curves (Roc) showed that the areas under the curves for MMP3, MMP9, and lncRNA ILF3AS1 as well as the fold-change for miRNA-212 were 0.659, 0.738, 0.656, and 0.965, respectively. Brain lesions were detected in 15 patients (30%) with epilepsy, whereas the remaining 35 patients (70%) had normal results. Conclusion: Serum levels of the lncRNA ILF3AS1 among children with epilepsy were higher than those in the control group and were associated with upregulation of both MMP3 and MMP9 as well as downregulation of miRNA-212 expressions, suggesting their predictive utility in monitoring the development of epilepsy; this also means that a treatment plan focusing on the ILF3AS1/miRNA-212/MMP3/MMP9 axis could be an effective strategy for treating epilepsy.

Successful Treatment of Angiolymphoid Hyperplasia with Eosinophilia Associated with Scalp Demodicosis Using Cryotherapy and Topical Metronidazole.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare, benign, vasoproliferative tumour. We report a 25-year-old female patient who reported in 2021 to a dermatology clinic in Rustaq, Oman, with multiple, grouped, erythematous dome-shaped papules and nodules of 6 months duration on the left temporo-occipital region. Biopsy findings were consistent with a diagnosis of ALHE with evidence of Demodex mite infestation in the sebaceous ducts. The patient demonstrated significant improvement following 7 weeks of treatment with multiple cryotherapy sessions and topical application of metronidazole gel. This case suggests that scalp demodicosis may represent a novel trigger for the development of ALHE.

Bimetallic MOF-based electrochemical sensor for determination of paracetamol in spiked human plasma.

Metal-organic frameworks (MOFs) with their exceptional properties have the potential to revolutionize the field of electrochemistry and pave the way for new and exciting applications. MOFs is an excellent choice as an active electrocatalyst component in the fabrication of electrochemical sensors. Here, bimetallic NiCo-MOFs, monometallic Ni-MOFs, and Co-MOFs were fabricated to modify the carbon paste electrode. Moreover, the ratio between Co and Ni within the bimetallic MOFs was optimized. Our aim in this work is to synthesize different compositions from bimetallic MOFs and systematically compare their catalytic activity with mono-metallic MOFs on paracetamol. The structure and properties of the 2D NiCo-MOFs were characterized by scanning electron microscope, X-ray photoelectron spectroscopy, Fourier transform infrared, and electrochemical method. Bimetallic Ni0.75Co0.25-MOFs modified carbon paste sensor displayed the optimum sensing performance for the electrochemical detection of paracetamol. A linear response over the range 6.00 × 10- 7 to 1.00 × 10- 4 M with a detection limit of 2.10 × 10- 8 M was obtained. The proposed method was applied to detect paracetamol in spiked human plasma and to determine paracetamol in the presence of its major toxic impurity, p-aminophenol. These findings suggest the considerable potential use of the newly developed sensor as a point-of-care tool for detecting paracetamol and p-aminophenol in the future.

Green Innovation and Synthesis of Honeybee Products-Mediated Nanoparticles: Potential Approaches and Wide Applications.

Bee products, abundant in bioactive ingredients, have been utilized in both traditional and contemporary medicine. Their antioxidant, antimicrobial, and anti-inflammatory properties make them valuable for food, preservation, and cosmetics applications. Honeybees are a vast reservoir of potentially beneficial products such as honey, bee pollen, bee bread, beeswax, bee venom, and royal jelly. These products are rich in metabolites vital to human health, including proteins, amino acids, peptides, enzymes, sugars, vitamins, polyphenols, flavonoids, and minerals. The advancement of nanotechnology has led to a continuous search for new natural sources that can facilitate the easy, low-cost, and eco-friendly synthesis of nanomaterials. Nanoparticles (NPs) are actively synthesized using honeybee products, which serve dual purposes in preventive and interceptive treatment strategies due to their richness in essential metabolites. This review aims to highlight the potential role of bee products in this line and their applications as catalysts and food preservatives and to point out their anticancer, antibacterial, antifungal, and antioxidant underlying impacts. The research used several online databases, namely Google Scholar, Science Direct, and Sci Finder. The overall findings suggest that these bee-derived substances exhibit remarkable properties, making them promising candidates for the economical and eco-friendly production of NPs.

Population status, habitat preferences and predictive current and future distributions of three endangered Silene species under changing climate.

One of the most crucial steps in the practical conservation of endangered endemic mountain plants is to address their population size status and habitat requirements concurrently with understanding their response to future global warming. Three endangered Silene species-Silene leucophylla Boiss., S. schimperiana Boiss., and S. oreosinaica Chowdhuri-in Egypt were the focus of the current study. These species were examined for population status change, habitat quality variables (topography, soil features, and threats), and predictive current and future distributions. To find population size changes, recent field surveys and historical records were compared. Using Random Forest (RF) and Canonical Correspondence Analysis (CCA), habitat preferences were assessed. To forecast present-day distribution and climate change response, an ensemble model was used. The results reported a continuous decline in the population size of the three species. Both RF and CCA addressed that elevation, soil texture (silt, sand, and clay fractions), soil moisture, habitat-type, chlorides, electric conductivity, and slope were among the important variables associated with habitat quality. The central northern sector of the Saint Catherine area is the hotspot location for the predictive current distribution of three species with suitable areas of 291.40, 293.10, and 58.29 km2 for S. leucophylla, S. schimperiana, and S. oreosinaica, respectively. Precipitation-related variables and elevation were the key predictors for the current distribution of three Silene species. In response to climate change scenarios, the three Silene species exhibited a gradual contraction in the predictive suitable areas with upward shifts by 2050 and 2070. The protection of these species and reintroduction to the predicted current and future climatically suitable areas are urgent priorities. Ex-situ conservation and raised surveillance, as well as fenced enclosures may catapult as promising and effective approaches to conserving such threatened species.

NLRP3 (rs10754558) gene polymorphism and tumor necrosis factor alpha as predictors for disease activity and response to methotrexate and adalimumab in psoriasis.

BACKGROUND: Psoriasis has a global prevalence of 1-3%, with variations observed across different ethnic groups and geographical areas. Disease susceptibility and response to anti-tumor necrosis factor-α (TNFα) drugs suggest different genetic regulatory mechanisms which may include NLR family pyrin domain containing 3 (NLRP3) polymorphism. Evaluation of the NLRP3 gene polymorphism, the serum level of CRP and TNFα in psoriasis patients and assessment of the NLRP3 (rs10754558) gene polymorphism, CRP and TNFα with disease severity and their role as biomarkers for response to Methotrexate and Adalimumab in psoriasis. The study had a total of 75 patients diagnosed with psoriasis vulgaris, who were compared to a control group of 75 healthy individuals. RESULTS: There was a highly significant difference in NLRP3 genotypes and alleles distribution between psoriasis patients and controls (P = 0.002,0.004). The heterozygote genotype GC (OR = 3.67,95%CI:1.75-7.68, P = 0.0006), was linked with increased risk of psoriasis. Additionally, The GC genotype was significantly associated with nonresponse to psoriasis therapy (OR = 11.7,95%CI:3.24-42.28, P = 0.0002). Regarding serum CRP and TNFα levels, there was a highly statistically significant difference between psoriasis patients and controls (P < 0.0001), and there was also a highly statistically significant difference between responders and non-responders in psoriasis patients regarding PASI 50 (P < 0.0001). CONCLUSIONS: The NLRP3 (rs10754558) genotypes GC was associated with the severe form of psoriasis and with nonresponse to psoriasis medication. Therefore, NLRP3 (rs10754558) gene polymorphism is an important prognostic biomarker in psoriasis patients. The serum TNFα can be used as a predictor for response to therapy in psoriasis patients. More research for evaluation of role of the NLRP3 gene polymorphism in the genetic risks and treatment outcomes associated with psoriasis is still required.

A Comprehensive Review of AI Diagnosis Strategies for Age-Related Macular Degeneration (AMD).

The rapid advancement of computational infrastructure has led to unprecedented growth in machine learning, deep learning, and computer vision, fundamentally transforming the analysis of retinal images. By utilizing a wide array of visual cues extracted from retinal fundus images, sophisticated artificial intelligence models have been developed to diagnose various retinal disorders. This paper concentrates on the detection of Age-Related Macular Degeneration (AMD), a significant retinal condition, by offering an exhaustive examination of recent machine learning and deep learning methodologies. Additionally, it discusses potential obstacles and constraints associated with implementing this technology in the field of ophthalmology. Through a systematic review, this research aims to assess the efficacy of machine learning and deep learning techniques in discerning AMD from different modalities as they have shown promise in the field of AMD and retinal disorders diagnosis. Organized around prevalent datasets and imaging techniques, the paper initially outlines assessment criteria, image preprocessing methodologies, and learning frameworks before conducting a thorough investigation of diverse approaches for AMD detection. Drawing insights from the analysis of more than 30 selected studies, the conclusion underscores current research trajectories, major challenges, and future prospects in AMD diagnosis, providing a valuable resource for both scholars and practitioners in the domain.

Osteocalcin, miR-143, and miR-145 Expression in Long-Standing Type 1 Diabetes Mellitus and Their Correlation with HbA1c.

Inadequate management and control of hyperglycemia predisposes diabetic patients to a wide range of complications. Thus, this opens new windows for exploring and scrutinizing novel candidate biomarkers. This study was designed to scrutinize the relationship between HbA1c, osteocalcin, calcium, phosphorus, and expression levels of miR-143 and miR-145 in individuals with T1DM and explore their correlations and diagnostic potential for T1DM. 120 unrelated participants were included (i.e., 90 participants with type 1 diabetes mellitus and 30 healthy controls) and were allocated into two groups. Participants with T1DM were allocated into three subgroups (i.e., below 1 year, 1-8 years, and over 8 years) based on diabetic duration. Participants with T1DM experienced noticeable HbA1c elevation. However, osteocalcin, phosphorus, and calcium profiles notably declined in participants with diabetes compared with those in healthy controls. Moreover, the expression levels of miR-143 and miR-145 decreased in participants with diabetes with a significant difference between participants with diabetes and healthy controls. Additionally, significant alterations in HbA1c, osteocalcin, phosphorus, and calcium profiles and expression levels of miR-143 and miR-145 were observed with increasing diabetic duration (T1DM > 8 years compared with those with a diabetes duration of less than 1 year). This study suggests that miR-143 and miR-145 are prospective biomarkers of diabetes mellitus, which may help predict the progression of complications.

The diagnostic accuracy of community spine radiology for adolescent idiopathic scoliosis brace candidates.

PURPOSE: The study aims to establish the diagnostic accuracy of community spine x-rays for brace candidates. METHODS: A review of adolescent idiopathic scoliosis patients seen for initial visit at a tertiary care pediatric hospital was conducted (n = 170). The index test was the pre-referral community spine x-ray interpreted by a community radiologist. Measures of diagnostic accuracy for the index test were determined against the reference standard if images were obtained within 90 days (n = 111). The reference standard was the 3-foot standing EOS spine x-ray evaluated by spine specialists. Diagnostic criterion for a brace candidate was dichotomized by Cobb angle range (25-40°) according to Scoliosis Research Society criteria. Risser stage was not included given significant missing data in index reports. To mitigate the uncertainty around true progression, sensitivity analyses were conducted on a sub-sample of data when index test was within 60 days of the reference standard (n = 67). RESULTS: Accuracy of the community spine x-ray to detect a brace candidate was 65.8% (95% CI 56.2-74.5). Sensitivity of the index test was 65.4% with a false negative rate of 34.6%. Specificity was 66.1% with a false positive rate of 33.9%. Positive and negative predictive values were 63.0% and 68.4%, respectively. Of the total number of brace candidates (n = 52), 32.7% were missed because of underestimation in Cobb angle (95% CI 21.5-46.2). The proportion of missed brace candidates because of underestimation was unchanged with 60-day data (p = 0.37). CONCLUSIONS: Inaccuracies in community spine radiology may lead to missed opportunities for non-operative treatment.

The effect of post-match fatigue on physical performance in adolescent soccer players.

BACKGROUND: Soccer involves many physically challenging actions and engaging in such activities can induce a decline in performance due to physical fatigue which predisposes players to develop injuries. The present study aimed to examine the impact of post-match fatigue on functional performance and Inter-Limb Asymmetry Index (LSI) in adolescent soccer players. METHODS: Thirty-eight adolescent male soccer players (15-18 years) completed a battery of functional performance measures (Rate of Perceived Exertion (RPE) scale, 10 m sprint, agility T-test, and Single leg hop for distance (SLHD) test). The data collection started prior to a soccer match and consisted of two testing sessions; two hours before the match, while the subsequent testing session was performed within two hours immediately following the match. RESULTS: The study results revealed a significant effect of post-match fatigue on change of direction abilities and SLHD (moderate effect size). However, no significant differences were observed in the 10 m sprint test and LSI (P>0.05). CONCLUSIONS: Functional performance measures such as agility test and SLHD test can detect physical ability changes due to post-match fatigue in adolescent soccer players. The study findings offer insightful and practical information on the importance of employing field-based functional performance measures in monitoring players' recovery following a game.

Sustainable kitchen wastewater treatment with electricity generation using upflow biofilter-microbial fuel cell system.

The microbial fuel cell (MFC) is considered a modern technology used for treating wastewater and recovering electrical energy. In this study, a new dual technology combining MFC and a specialized biofilter was used. The anodic materials in the system were crushed graphite, either without coating (UFB-MFC) or coated with nanomaterials (nano-UFB-MFC). This biofilter served as a barrier to retain and remove turbidity and suspended solids, while also facilitating the role of bacteria in the removal of organic pollutants, phosphates, nitrates, sulfates, oil and greases. The results demonstrated that both systems exhibited high efficiency in treating kitchen wastewater, specifically greywater and dishwashing wastewater with high detergent concentrations. The removal efficiencies of COD, oil and grease, suspended solids, turbidity, nitrates, sulfates, and phosphates in first UFB-MFC were found to be 88, 95, 89, 86, 87, 75, and 94%, respectively, and in Nano-UFB-MFC were 86, 99, 95, 91, 81, 88, and 95%, respectively, with a high efficiency in recovering bioenergy reaching a value of 1.8 and 1.5 A m-3, respectively. The results of this study demonstrate the potential for developing MFC and utilizing it as a domestic system to mitigate pollution risks before discharging wastewater into the sewer network.

The Cytoprotective and Cytotoxic Functions of Autophagy in Response to mTOR Inhibitors.

The inhibitors of mammalian target of rapapmycin (mTOR), everolimus, temsirolimus and rapamycin, have a wide range of clinical utility; however, as is inevitably the case with other chemotherapeutic agents, resistance development constrains their effectiveness. One putative mechanism of resistance is the promotion of autophagy, which is a direct consequence of the inhibition of the mTOR signaling pathway. Autophagy is primarily considered to be a cytoprotective survival mechanism, whereby cytoplasmic components are recycled to generate energy and metabolic intermediates. The autophagy induced by everolimus and temsirolimus appears to play a largely protective function, whereas a cytotoxic function appears to predominate in the case of rapamycin. In this review we provide an overview of the autophagy induced in response to mTOR inhibitors in different tumor models in an effort to determine whether autophagy targeting could be of clinical utility as adjuvant therapy in association with mTOR inhibition.

Novel HER2-based multi-epitope vaccine (HER2-MEV) against HER2-positive breast cancer: In silico design and validation.

Breast cancer (BC) continues to be the malignancy with the highest diagnosis rate worldwide. Between 15 % and 30 % of BC patients show overexpressed human epidermal growth factor receptor 2 (HER2), which is linked to poor clinical results in terms of invasiveness and recurrence risk. Passive immunity-based therapeutic approaches for treating HER2-enriched BC, are not effective and significant problems need to be tackled. Constructing multi-epitope vaccines is favored over single-epitope vaccines due to its ability to induce immunity against a variety of antigenic targets which will improve the efficacy of the vaccine. The current study describes a multi-epitope vaccine from HER2 protein against HER2-positive BC using several immunoinformatic techniques to achieve a potent and durable immune response. Nine Cytotoxic T lymphocytes (CTL) and five Helper T lymphocytes (HTL) epitopes were predicted and validated from HER2 protein using in silico tools. The expressed protein of the designed vaccine is predicted to be highly thermostable with better solubility. The predicted vaccine 3D structure was validated by ProSA servers and by the ERRAT server. Molecular docking analysis revealed a high binding affinity and stability of the designed vaccine with MHCI and TLR-2, 4, 7, and 9 receptors. The analysis of the C-ImmSim server revealed that the novel vaccine construct had the ability to elicit robust anti-cancerous innate, humoral, and cell-mediated immune responses. The vaccine can be a suitable option for HER2-positive BC patients and other patients with HER2-positive cancers to evoke immune responses. However, in vitro and in vivo experiments are needed to assess its effectiveness and safety.

Effect of interleukin 6 (IL-6) on sperm quality, kinematic parameters, acrosome integrity, apoptosis, ultrastructure, and molecular docking in cryopreserved ram spermatozoa.

Sperm cryopreservation can lead to subfertility due to potential damage to sperm DNA, membranes, and overall motility caused by the freeze-thaw process. Interleukin-6 (IL-6) is a versatile cytokine with various roles in reproductive processes. However, the impacts of IL-6 supplementation on cryopreserved ram sperm have not been thoroughly investigated. Therefore, this study aims to assess the influence of IL-6 on the sperm quality of cryopreserved ram sperm. Ram semen was collected, pooled, and extended with tris-citrate soybean lecithin extender supplemented with 0, 50, 100, and 200 ng/mL of IL-6. The samples experienced a standard freezing protocol, and sperm quality, kinematic parameters, ultrastructure, and molecular docking of cryopreserved ram spermatozoa were evaluated. The results showed that sperm kinematics, viability, progressive motility, and membrane integrity were significantly enhanced by the addition of 100 or 200 ng of IL-6/mL (p < 0.05). Semen supplemented with 100 or 200 ng/mL of IL-6 also exhibited higher percentages of sperm kinematics, including DAP, DCL, DSL, VSL, VAP, VCL, and ALH, compared to other groups (p < 0.05). IL-6 supplementation enhanced acrosome integrity, and reduced caspase-3 activity in post-thawed ram spermatozoa (p < 0.05) compared to untreated group. Supplementation with IL-6 (200 ng/mL) significantly decreased oxidative biomarkers (NO, MDA, and H2O2) (p < 0.001) and improved total antioxidant capacity (p < 0.05). The percentage of sperm damage (tail, head, and midpiece) was significantly reduced by IL-6 supplementation (p < 0.05). Electron micrographs showed that supplementation with 100 or 200 ng/mL IL-6 protected acrosome stability, plasma membrane integrity, and sustained the ultrastructure integrity of cryopreserved ram spermatozoa. The docking exploration indicates a higher binding affinity with sperm function biomarkers, including caspase 3, BCL2, and PSMA6, with binding energies of - 52.30 kcal/mol, - 56.04 kcal/mol, and - 57.06 kcal/mol, respectively. In conclusion, the addition of IL-6 to the freezing extender can enhance the post-thaw quality of cryopreserved ram spermatozoa.

The effect of aging on the translucency of contemporary zirconia generations: in-vitro study.

BACKGROUND: The translucency of different zirconia generations at each time point after thermocycling aging is still lacking. METHODS: Four zirconia materials were used with a total of 60 samples produced from monolithic third generation (5Y) 5 mol% yttria-stabilized zirconia polycrystalline ceramic and fourth generation zirconia (4Y) 4 mol% yttria-stabilized zirconia polycrystalline ceramic, represented by [group1:[CM-5Y] Ceramill Zolid fx (3rd generation zirconia) (Amann Girrbach, Koblach, Austria), group 2:[CM-4Y] Ceramill Zolid HT + (4th generation zirconia) (Amann Girrbach, Koblach, Austria), group 3:[CC-5Y] Cercon XT/ML (Dentsply Sirona, Germany) (3rd generation), and group 4:[CC-4Y] Cercon HT/ML (Dentsply Sirona, Germany) (4th generation)]. The L*a*b* figures were measured by using a spectrophotometer at baseline and after 10,000, 30,000, and 50,000 cycles of thermocycling. At each interval, the translucency of the samples was estimated by using the translucency formula CIEDE2000. The Scheffe post-hoc compared differences among each of the four materials. The Repeated measures ANOVA tested the differences between the materials at each of the different thermocycling intervals (p < .001). Data analyses were evaluated at a significance level of p < .05 (CI 95%). RESULTS: Two-way ANOVA revealed that at baseline the third and fourth generation's zirconia showed statistically significant differences in translucency (P < .001). Translucency values at baseline and after thermocycling exhibited statistically significant changes (p = .003). At each of the time interval; CM-4Y had the highest translucency values followed by CM-5Y, CC-4Y and CC-5Y had the least translucency values. CONCLUSIONS: The third and fourth generations of zirconia displayed different translucencies. Thermocycling affected the translucency of both third and fourth generations of zirconia. At each of the time intervals group 2:[CM-4Y] had the highest TP followed by group1:[CM-5Y], while, group 3:[CC-5Y] and group 4:[CC-4Y] had the least TP.

Development of Response Surface Approach for Determination of Paracetamol, Chlorpheniramine Maleate, Caffeine and Ascorbic Acid by Green HPLC Method: A Desirability-Based Optimization.

Design of experiment is an efficient and cost-effective tool to optimize the chromatographic separation of a multicomponent mixture. The central composite design was conducted to develop and optimize a green high performance liquid chromatography (HPLC) method for simultaneous quantitation of a quaternary mixture of paracetamol, chlorpheniramine maleate, caffeine and ascorbic acid in their pharmaceutical dosage form as well as the determination of their dissolution profile. A five-level three-factor model was performed to investigate the effect of mobile phase composition, pH and flow rate on enhanced resolution and short run time. Analysis was performed using a Kinitex EVO C18 column and a mobile phase composed of methanol: 0.02 M phosphate buffer pH 3.3 (34:66, v/v) at 1.0 mL/min using photodiode array detection. Optimum chromatographic separation was achieved in <6 min with a desirability of 0.999. Linearity was achieved over a range of 1.00-300.00, 1.00-50.00, 2.00-50.00 and 2.00-100.00 µg/mL for paracetamol, chlorpheniramine maleate, caffeine and ascorbic acid, respectively, with a limit of detection (<0.1 µg/mL). The greenness profile was evaluated using the analytical eco-scale and Analytical GREEnness Metric Approach with values of 81 and 0.77, respectively.

Novel Variants Linked to the Prodromal Stage of Parkinson's Disease (PD) Patients.

BACKGROUND AND OBJECTIVE: The symptoms of most neurodegenerative diseases, including Parkinson's disease (PD), usually do not occur until substantial neuronal loss occurs. This makes the process of early diagnosis very challenging. Hence, this research used variant call format (VCF) analysis to detect variants and novel genes that could be used as prognostic indicators in the early diagnosis of prodromal PD. MATERIALS AND METHODS: Data were obtained from the Parkinson's Progression Markers Initiative (PPMI), and we analyzed prodromal patients with gVCF data collected in the 2021 cohort. A total of 304 participants were included, including 100 healthy controls, 146 prodromal genetic individuals, 21 prodromal hyposmia individuals, and 37 prodromal individuals with RBD. A pipeline was developed to process the samples from gVCF to reach variant annotation and pathway and disease association analysis. RESULTS: Novel variant percentages were detected in the analyzed prodromal subgroups. The prodromal subgroup analysis revealed novel variations of 1.0%, 1.2%, 0.6%, 0.3%, 0.5%, and 0.4% for the genetic male, genetic female, hyposmia male, hyposmia female, RBD male, and RBD female groups, respectively. Interestingly, 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300, and PPP6R2) that were recently detected in PD patients were detected in the prodromal stage of PD. CONCLUSIONS: Genetic biomarkers are crucial for the early detection of Parkinson's disease and its prodromal stage. The novel PD genes detected in prodromal patients could aid in the use of gene biomarkers for early diagnosis of the prodromal stage without relying only on phenotypic traits.