Comparing Intradermal (ID) Rabies Vaccination with Conventional IM Regimen on Humoral Response of New Zealand White Rabbits for the Production of Animal-Derived Polyclonal Antibodies.

In developing countries, it is imperative to implement cost-effective strategies for animal humoral response development in the production of antiserum. This study compared the effect of immunization regimens on the humoral immune response of New Zealand White (NZW) rabbits (N = 24) using cell culture rabies vaccine (CCRV) through intradermal (ID) and traditional intramuscular (IM) routes. The rabbits were divided into three experimental groups: (a) IPC-R2 with a two-site one-week regimen; (b) TRC-R3 with a two-site twenty-eight-day regimen; and (c) Alternate-R4 with a four-site one-week regimen. These regimens were then compared to the standard IM schedule of five doses of rabies vaccine administered at days 0, 3, 7, 14, and 28 in control group R-1. The results were evaluated at days 14 and 35 postvaccination using rabies-specific Platelia II™ ELISA kit method. The results showed a better response to the ID regimen than the IM route regarding immunogenicity and volume consumption of the vaccine. The three selected ID regimes showed significantly higher mean titer values than the control IM regimen group R-1 (p < 0.001). The study aims to explore simple immunization strategies to enhance the RV-specific antibody titers for immunization donor animals. This method would produce polyclonal antibodies and strengthen local production of polyclonal antibodies in Pakistan to deal with vaccine and rabies immunoglobulin (RIG) shortage, thus providing effective postexposure prophylaxis (PEP) for better control of rabies in developing countries.

Multiple inborn errors of type I IFN immunity in a 33-year-old male with a fatal case of COVID-19.

The host genetic inborn errors of immunity (IEIs) have been shown to contribute to susceptibility to life-threatening coronavirus disease 2019 (COVID-19), as it had been associated previously with other viral infections. Most genetic association studies have described IEIs as a monogenic defect, while there have been no reports of patients with multiple inherited immune deficiencies. This is a complex case of IEIs predisposing to severe viral infections in an unvaccinated 33-year-old male patient. The patient was admitted with no respiratory symptoms, showed a SARS-CoV-2 PCR positive test on the second day of admission, started developing progressive lung consolidation within three days of hospitalization, and was moved from non-invasive to mechanical ventilation within 12 days of hospitalization. Impaired production of type I IFN was detected in patient PBMCs treated with poly(I:C), at both mRNA and protein levels. Whole exome sequencing revealed three mutations across type I IFN production pathway, which were predicted to be loss-of-function (pLOF). The three mutations were predicted to predispose to severe viral infections: monoallelic R488X TLR3, monoallelic His684Arg TLR3, and biallelic Val363Met IRF3. Functional analysis confirmed that all these mutations dysregulated the type I IFN pathway. Evaluation of TLR3 and IRF3 IFN-ß1 luciferase reporter activity showed a hypomorphic suppression of function. TOPO TA cloning was used to ascertain the positioning of both TLR3 variants, indicating that both variants were on the same allele. We have described a unique complex IEI patient with multiple mutations, particularly along type I IFN production pathway.

Solar desalination system for fresh water production performance estimation in net-zero energy consumption building: A comparative study on various machine learning models.

This study employs diverse machine learning models, including classic artificial neural network (ANN), hybrid ANN models, and the imperialist competitive algorithm and emotional artificial neural network (EANN), to predict crucial parameters such as fresh water production and vapor temperatures. Evaluation metrics reveal the integrated ANN-ICA model outperforms the classic ANN, achieving a remarkable 20% reduction in mean squared error (MSE). The emotional artificial neural network (EANN) demonstrates superior accuracy, attaining an impressive 99% coefficient of determination (R2) in predicting freshwater production and vapor temperatures. The comprehensive comparative analysis extends to environmental assessments, displaying the solar desalination system's compatibility with renewable energy sources. Results highlight the potential for the proposed system to conserve water resources and reduce environmental impact, with a substantial decrease in total dissolved solids (TDS) from over 6,000 ppm to below 50 ppm. The findings underscore the efficacy of machine learning models in optimizing solar-driven desalination systems, providing valuable insights into their capabilities for addressing water scarcity challenges and contributing to the global shift toward sustainable and environmentally friendly water production methods.

Risk factors and early preventive measures for long COVID in non-hospitalized patients: analysis of a large cohort in the United Arab Emirates.

OBJECTIVES: Long COVID is characterized by persistent symptoms lasting for 4 weeks or more following the acute infection with SARS-CoV-2. Risk factors for long COVID and the impact of pre-COVID vaccination and treatment during acute COVID-19 remain uncertain. This study aimed to investigate patient-specific factors associated with long COVID in a large cohort of non-hospitalized adult patients with mild to moderate COVID-19 in Dubai. STUDY DESIGN: Cohort study. METHODS: The study included 28,375 non-hospitalized adult patients diagnosed with mild to moderate COVID-19 between January 1, 2021, and September 31, 2022, in Dubai, who were followed up for 90 days. The presence of long COVID symptoms was documented by physicians during patient visits to the family medicine department. Furthermore, long COVID-related risk factors were collected and analyzed, including patient demographics, comorbidities, pre-COVID vaccination status, and the COVID-related treatments received during the acute phase of the illness. Cox proportional hazard models were applied for the statistical analysis. RESULTS: Among the cohort, 2.8% of patients experienced long COVID symptoms during the 90-day follow-up. Patients with long COVID tended to be younger, female, and of Caucasian race. Common symptoms included fatigue, muscle pain, respiratory symptoms, abdominal and neurological symptoms, allergic reactions, skin rashes, and hair loss. Risk factors for long COVID were identified as diabetes mellitus, asthma, and Vitamin D deficiency. Females and Caucasians had a higher risk of long COVID during the pre-Omicron period compared to the Omicron period. Pre-COVID vaccination was associated with a reduced risk of long COVID in all patient subgroups. Treatment with favipiravir or sotrovimab during the acute phase of COVID-19 was linked to a decreased risk of long COVID, although favipiravir showed limited effectiveness in the high-risk group. CONCLUSION: This study contributes to the existing knowledge by identifying risk factors for long COVID among non-hospitalized patients and emphasizing the potential benefits of pre-COVID vaccination and timely treatment.

Augmenting authenticity for non-invasive in vivo detection of random blood glucose with photoacoustic spectroscopy using Kernel-based ridge regression.

Photoacoustic Spectroscopy (PAS) is a potential method for the noninvasive detection of blood glucose. However random blood glucose testing can help to diagnose diabetes at an early stage and is crucial for managing and preventing complications with diabetes. In order to improve the diagnosis, control, and treatment of Diabetes Mellitus, an appropriate approach of noninvasive random blood glucose is required for glucose monitoring. A polynomial kernel-based ridge regression is proposed in this paper to detect random blood glucose accurately using PAS. Additionally, we explored the impact of the biological parameter BMI on the regulation of blood glucose, as it serves as the primary source of energy for the body's cells. The kernel function plays a pivotal role in kernel ridge regression as it enables the algorithm to capture intricate non-linear associations between input and output variables. Using a Pulsed Laser source with a wavelength of 905 nm, a noninvasive portable device has been developed to collect the Photoacoustic (PA) signal from a finger. A collection of 105 individual random blood glucose samples was obtained and their accuracy was assessed using three metrics: Root Mean Square Error (RMSE), Mean Absolute Difference (MAD), and Mean Absolute Relative Difference (MARD). The respective values for these metrics were found to be 10.94 (mg/dl), 10.15 (mg/dl), and 8.86%. The performance of the readings was evaluated through Clarke Error Grid Analysis and Bland Altman Plot, demonstrating that the obtained readings outperformed the previously reported state-of-the-art approaches. To conclude the proposed IoT-based PAS random blood glucose monitoring system using kernel-based ridge regression is reported for the first time with more accuracy.

The Effects of Six Weeks Pulmonary Rehabilitation on Functional and Psychological Outcomes in Long-COVID Patients: Preliminary Results from Serbian Single Center Study.

Background and Objectives: In this study, we aimed to evaluate the effects of six weeks of pulmonary rehabilitation on functional and psychological outcomes in long-COVID patients. Material and Methods: The prospective clinical study included 46 patients that were diagnosed with COVID-19. A respiratory rehabilitation program was implemented for six weeks. Further valuables were tested before the beginning of the rehabilitation program (admission) and six weeks after (discharge): SpO2, heart rate, respiratory rate, Visual Analogue Scale (VAS) score, Borg score, Sit-to-Stand (StS) test number of repetition, distance of 6-Minute Walking Test (6MWT), Patient Health Questionnaire (PHQ) 9 score and Generalized anxiety disorder (GAD) anxiety score. These parameters were tested before the rehabilitation program on admission and at discharge and after the rehabilitation program on admission and at discharge. The results were presented with standard descriptive and analytical methods. Differences between the continuous variables before and after physical rehabilitation intervention were tested using the Wilcoxon test. Graphical analysis is presented with a box plot. Results: On discharge, in comparison with admission, the values of SpO2 were significantly lower (p = 0.007) before the 6MWT, and VAS scores were significantly higher (p = 0.036), while after the 6MWT, VAS scores were significantly lower (p < 0.001) as were Borg scores (p = 0.016). On discharge, in comparison with admission, the respiratory rate was significantly higher (p = 0.005) before the StS test, and Borg scores were significantly lower (p = 0.001), while after the StS test, SpO2 levels were significantly higher (p = 0.036) and VAS scores were significantly lower (p < 0.001), as were Borg scores (p = 0.008). After discharge, the values of the StS test were significantly higher (p = 0.011), PHQ9 scores were significantly lower (p < 0.001) and GAD anxiety scores were significantly lower as well (p = 0.005), while the distances measured in meters on the 6MWT were significantly increased (p < 0.001). Conclusions: A structured rehabilitation program in our study was shown to have beneficial effects on physiological, psychological and functional improvements in patients with long-COVID, and therefore it is advisable for these patients.

Clinical pharmacist interventions in an intensive care unit reduces ICU mortality at a tertiary hospital in Dubai, United Arab Emirates.

Background: Drug-related problems (DRPs) are prevalent in critical care settings and can be life-threatening. Involving clinical pharmacists (CP) within the critical care team is recommended to optimize therapy and improve patient survival. Objective: To classify DRPs identified by a CP in the Intensive Care Unit (ICU) and to assess the impact of CP interventions accepted by physicians on the length of ICU stay and in-hospital survival. Methods: This study was conducted prospectively at the Medical ICU of Rashid Hospital, a tertiary hospital in Dubai, over a 16-month period from September 2021 to December 2022. The study included patients admitted to ICU during the study period. CP interventions were documented, and DRPs were classified using the modified Pharmaceutical Care Network Europe V.9.1. Results: During the study period, 1004 interventions were recommended for 200 patients. The majority of these interventions, 92% (n = 922), received physician acceptance, and 82% (n = 820) were fully implemented by the physician. In total, 1033 drug-related problems (DRPs) were identified, with a median of 3 DRPs per patient. The most common DRPs was drug selection (61%), followed by dose selection (22%). There were 337 DRPs related to antimicrobial agents. Interestingly, we noted that when we adjusted for patients' demographic data and the Glasgow Coma Scale severity score, patients who received >4 implemented interventions exhibited lower cumulative hazard of death within 90 days of their ICU stay in comparison to their counterparts (adjusted Hazard Ratio: 0.10, 95% CI of 0.02-0.41; P = 0.027). Conclusion: The study emphasizes the critical role of CP in the ICU, addressing DRPs, and enhancing overall patient care. Furthermore, it highlights the potential impact of pharmacist interventions in improving patient survival outcomes. This underscores the importance of implementing CP services in ICUs across the UAE.

Salivary autoantibodies to type I IFNs: Mirror plasma levels, predispose to severe COVID-19, and enhance feasibility for clinical screening.

BACKGROUND: Autoantibodies have been demonstrated to dampen the interferon (IFN) response in viral infections. Elevated levels of these preexisting autoantibodies (aAbs) decrease basal interferon levels, increasing susceptibility to severe infections. OBJECTIVES: This study aimed to evaluate the prevalence of type I IFN aAbs in both plasma and saliva from COVID-19 patients, analyze their neutralizing activity, and examine their associations with clinical outcomes, including the need for mechanical ventilation and in-hospital mortality. METHODS: Prospective analyses of patients admitted to intensive care units in three UAE hospitals from June 2020 to March 2021 were performed to measure aAbs using enzyme-linked immunosorbent assay (ELISA), assess aAbs activity via neutralization assays, and correlate aAbs with clinical outcomes. RESULTS: Type I IFN aAbs (α2 and/or ω) were measured in plasma samples from 213 ICU patients, and positive results were obtained for 20 % (n = 42) of the patients, with half exhibiting neutralizing activity. Saliva samples from a subgroup of 24 patients reflected plasma levels. In multivariate regression analyses, presence of type I IFN aAbs was associated with a higher need for mechanical ventilation (OR 2.58; 95 % CI 1.07-6.22) and greater in-hospital mortality (OR 2.40; 95 % CI 1.13 - 5.07; P = 0.022). Similarly, positive neutralizing aAbs (naAbs) were associated with a greater need for mechanical ventilation (OR 4.96; 95 % CI 1.12-22.07; P = 0.035) and greater odds of in-hospital mortality (OR 2.87; 95 % CI 1.05-7.89; P = 0.041). CONCLUSIONS: Type I IFN autoantibodies can be detected in noninvasive saliva samples, alongside conventional plasma samples, from COVID-19 patients and are associated with worse outcomes, such as greater mechanical ventilation needs and in-hospital mortality.

Mental health literacy and help-seeking behaviour among Egyptian undergraduates: a cross-sectional national study.

BACKGROUND: Mental health literacy (MHL) and help-seeking behaviors are pivotal in managing mental well-being, especially among Egyptian undergraduates. Despite the importance and prevalent psychological distress in this group, limited research has addressed MHL and associated behaviors in Egypt. This study aimed to assess the levels of MHL and help-seeking behavior among Egyptian university students. METHODS: A cross-sectional study was conducted across ten Egyptian universities during the academic year 2022-2023. A convenience sample of 1740 students was obtained through online questionnaires distributed via social media platforms. The survey comprised demographic characteristics, the Mental Health Literacy Scale (MHLS), and the General Help Seeking Behavior Questionnaire (GHSPQ). RESULTS: Among 1740 Egyptian undergraduates, medical students scored higher in recognizing disorders (p < 0.05), while non-medical students excelled in attitudes (p < 0.05). A strong correlation was observed between attitudes toward mental illness and total mental health literacy (coefficients of 0.664 and 0.657). Univariate analysis indicated a significant association with professional help-seeking (OR = 1.023). Females, individuals aged 21 or above, and non-medical students were more likely to seek mental health information (OR = 1.42, 1.82, 1.55 respectively). Help-seeking behavior for emotional problems was more inclined towards intimate partners, whereas suicidal thoughts prompted seeking professional help. CONCLUSION: The findings advocate for comprehensive mental health education, particularly in rural areas, and emphasis on the role of personal relationships in mental well-being. Implementing these insights could foster improved mental health outcomes and reduce related stigma in Egypt.

Rhino orbital cerebral mucormycosis: A life-threatening complication of coronavirus diseases 2019 in an uncontrolled diabetic patient.

Mucormycosis is a progressive and life-threatening disease that has been increasingly reported in patients infected by coronavirus diseases 2019 (COVID-19). We describe a case of rhino-orbital mucormycosis with central nervous system involvement resulting in bilateral blindness and intracranial extension in a patient with uncontrolled diabetes mellitus (DM) and mild COVID-19 infection. A 35-year-old obese male, recently diagnosed with DM, presented to the emergency department suffering from dizziness, headache, speech difficulty, and facial weakness. His glycosylated hemoglobin was 10.4% and his reverse transcriptase-polymerase chain reaction (PCR) test came positive for COVID-19. Ocular examination revealed left eye proptosis, ophthalmoplegia, and lid edema with no ocular movement. Imaging studies showed pansinusitis and periorbital and orbital cellulitis with intracranial involvement. Histopathology and biopsy examination confirmed mucormycosis. Medical management included glucose control and liposomal amphotericin B therapy. Septoplasty and functional endoscopic sinus surgery was performed as emergency procedures. The patient survived with bilateral blindness. In this case, we described the importance of considering mucormycosis in COVID-19 patients with uncontrolled diabetes, particularly those presenting with sinusitis, headache, and orbital edema symptoms. Despite intensive antifungal therapy and surgical intervention, it is a serious opportunistic fungal infection associated with long-term complications.

Effectiveness of functional electrical stimulation machine in managing neurological diseases - A retrospective study.

Background & Objective: Cerebrovascular Accident (CVA) or stroke, Spinal Cord injury can lead to neurological diseases resulting in major loss in motor function causing hemiplegia or tetraplegia. In 2019, according to The Global Burden of Diseases (GBD) CVA/Stroke is the second leading cause of death and the third leading cause of death and disability combined, globally. Its prevalence vary drastically among South Asian countries. The objective of this study was to determine the effectiveness of Functional Electrical Stimulation (FES) machine on neurologically impaired patients at the Physical Therapy department at IHHN, Karachi, Pakistan. Method: In this retrospective study data was extracted from August 2016 to February 2022 on patients with neurological symptoms i.e. hemiplegia or paraplegia with muscle power of two or less on Manual Muscle Testing (MMT). The parameters for evaluating patients progress pre and post treatment were MMT results and their mobility status. The number of sessions ranged between 40 to 100 sessions of Functional Electrical Stimulation (FES) provided on alternate days according to the patient's need. Result: Data of 51 patients who had completed their treatment were extracted and analyzed. The mean age of patients who completed treatment was 49.62 ± 17.26 years. Out of 51(100%), 30 (58.8%) were male and 21 (41.2%) were female. Pre- and post-treatment median (IQR) showed remarkable improvement in MMT of upper limb muscle (from 1.0 to 4.0) and lower limb muscle (from 2.0 to 4.0). Conclusion: FES cycling is an effective treatment for patients with neurological impairments, as it resulted in improvement in both upper and lower limb muscle strength, along with mobility status.

An Evaluation of Treatment Outcomes and Associated Factors in Nasopharyngeal Cancer Patients at a Tertiary Cancer Center in the United Arab Emirates.

Background and objective Nasopharyngeal carcinoma (NPC) presents a complex epidemiological pattern influenced by demographic characteristics, risk factors such as Epstein-Barr virus (EBV) infection, and smoking. Understanding the clinical profile and optimizing treatment strategies for NPC requires comprehensive analyses of these factors. In light of this, this study aimed to analyze the epidemiological patterns, histological characteristics, and treatment outcomes of NPC patients diagnosed and treated at a single center from 2016 to 2023. Materials and methods This retrospective study was conducted at Tawam Hospital in the United Arab Emirates (UAE), focusing on patients diagnosed with NPC. It involved the analysis of patient age distribution to identify epidemiological patterns, histological examination to classify NPC types according to WHO guidelines, and evaluation of treatment outcomes based on induction chemotherapy regimens and concurrent chemoradiotherapy protocols. The effectiveness of various chemotherapy combinations, particularly cisplatin and 5-fluorouracil (Cis+5FU), was assessed alongside the integration of advanced radiotherapy techniques like intensity-modulated radiotherapy (IMRT). Results In this study of 41 NPC patients, the age distribution varied widely, ranging from 10 to 74 years, with a mean age of >40 years. There was a significant male predominance (82.93%). Most patients were non-smokers (68.29%) and did not consume alcohol (92.68%), and there was a high prevalence of EBV positivity (100%). At diagnosis, 80.49% had no metastases. The primary treatment was chemotherapy induction, with a 73.17% uptake and a 92.68% completion rate, leading to a 65.85% complete response (CR) rate. No significant association was found between smoking status and treatment response (p=0.7657). Pathologically, non-keratinizing undifferentiated squamous carcinoma was the most common variant (75.61%). The Cis+5FU regimen was the most frequently employed method (56.67%), associated with a 76.47% CR rate. Concurrent chemotherapy was administered to 87.80% of patients, with the weekly Cis regimen being the most used one (56.09%), resulting in a significant CR rate. Combining radiation therapy with concurrent and induction chemotherapy yielded high CR rates (RT+cCT: 66.66%, RT+cCT+iCT: 80%). Survival analysis revealed the highest 36-month survival rate (46.43%) in the RT+cCT+iCT group, suggesting a potential benefit from incorporating induction chemotherapy into the treatment regimen. Conclusions This study illustrates the impact of demographic variables, EBV infection, and smoking on the development and treatment outcomes of NPC. It points to the success of customized chemotherapy and advanced radiotherapy strategies. Yet, it is limited by its retrospective nature and single-center focus, and hence we recommend multicentric studies to broaden the applicability of the results and improve NPC treatment approaches for varied patient groups.

Ciprofloxacin loaded PEG coated ZnO nanoparticles with enhanced antibacterial and wound healing effects.

Antimicrobial resistance is a worldwide health problem that demands alternative antibacterial strategies. Modified nano-composites can be an effective strategy as compared to traditional medicine. The current study was designed to develop a biocompatible nano-drug delivery system with increased efficacy of current therapeutics for biomedical applications. Zinc oxide nanoparticles (ZnO-NPs) were synthesized by chemical and green methods by mediating with Moringa olifera root extract. The ZnO-NPs were further modified by drug conjugation and coating with PEG (CIP-PEG-ZnO-NPs) to enhance their therapeutic potential. PEGylated ZnO-ciprofloxacin nano-conjugates were characterized by Fourier Transform Infrared spectroscopy, X-ray diffractometry, and Scanning Electron Microscopy. During antibacterial screenings chemically and green synthesized CIP-PEG-ZnO-NPs revealed significant activity against clinically isolated Gram-positive and Gram-negative bacterial strains. The sustainable and prolonged release of antibiotics was noted from the CIP-PEG conjugated ZnO-NPs. The synthesized nanoparticles were found compatible with RBCs and Baby hamster kidney cell lines (BHK21) during hemolytic and MTT assays respectively. Based on initial findings a broad-spectrum nano-material was developed and tested for biomedical applications that eradicated Staphylococcus aureus from the infectious site and showed wound-healing effects during in vivo applications. ZnO-based nano-drug carrier can offer targeted drug delivery, and improved drug stability and efficacy resulting in better drug penetration.

QbD-Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture.

Biomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)-loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa-nHA-GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box-Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, -20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine-B loaded nHA-GLT NPs demonstrates considerably higher cellular uptake by the murine-derived macrophages than free rhodamine-B solution. In vitro, cell-based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD-based approach has successfully led to the development of Tofa-nHA-GLT NPs with the potential to target inflamed arthritic joint.

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Machine Learning-Enabled NIR Spectroscopy. Part 3: Hyperparameter by Design (HyD) Based ANN-MLP Optimization, Model Generalizability, and Model Transferability.

Data variations, library changes, and poorly tuned hyperparameters can cause failures in data-driven modelling. In such scenarios, model drift, a gradual shift in model performance, can lead to inaccurate predictions. Monitoring and mitigating drift are vital to maintain model effectiveness. USFDA and ICH regulate pharmaceutical variation with scientific risk-based approaches. In this study, the hyperparameter optimization for the Artificial Neural Network Multilayer Perceptron (ANN-MLP) was investigated using open-source data. The design of experiments (DoE) approach in combination with target drift prediction and statistical process control (SPC) was employed to achieve this objective. First, pre-screening and optimization DoEs were conducted on lab-scale data, serving as internal validation data, to identify the design space and control space. The regression performance metrics were carefully monitored to ensure the right set of hyperparameters was selected, optimizing the modelling time and storage requirements. Before extending the analysis to external validation data, a drift analysis on the target variable was performed. This aimed to determine if the external data fell within the studied range or required retraining of the model. Although a drift was observed, the external data remained well within the range of the internal validation data. Subsequently, trend analysis and process monitoring for the mean absolute error of the active content were conducted. The combined use of DoE, drift analysis, and SPC enabled trend analysis, ensuring that both current and external validation data met acceptance criteria. Out-of-specification and process control limits were determined, providing valuable insights into the model's performance and overall reliability. This comprehensive approach allowed for robust hyperparameter optimization and effective management of model lifecycle, crucial in achieving accurate and dependable predictions in various real-world applications.

Friedelin and Glutinol induce neuroprotection against ethanol induced neurotoxicity in pup's brain through reduction of TNF-α, NF-kB, caspase-3 and PARP-1.

Ethanol administration triggers an inflammatory response that leads to a complex series of immune responses including the release of an excessive amount of inflammatory mediators particularly tumor necrosis factor (TNF-α) and nuclear factor-kB (NF-KB) which produce a large amount of reactive oxygen species. The inflammatory-induced cytotoxicity is increased when the PI3-kinase/Akt pathway is inhibited. Some studies have also shown that ethanol suppresses the PI3-kinase signaling pathway induced by receptor activation. Friedelin and Glutinol belong to pentacyclic triterpenoid class and are known for their anti-inflammatory and antioxidant properties. The present study was aimed to elucidate the effects of these phytoconstituents on one of the key ethanol-induced neuronal damage pathways. The pups having (5-7 g average body weight) were used and randomly divided into groups. The control and ethanol treated pups were administered 0.9% normal saline while treated pups received glutinol and friedelin (30 mg/kg subcutaneously) respectively. After four hours all the experimental animals were sacrificed and their brains were collected carefully for protein expression analysis of p-Akt, TNF-α, NF-KB, caspase-3 and PARP-1 employing immunoblotting technique. Hemolytic, DNA protection, chelating power and ß-carotene assays results revealed that freidelin and glutinol are safe for parenteral administration. Glutinol administration with ethanol significantly abridged the ethanol induced over expression of TNF-α, caspase-3 and PARP-1 in pup's brain. Similarly, freidelin attenuated the neurodegeneration by inhibiting the ethanol induced p-JNK and NF-kB expression in pups' brain. This protection may be attributed to the revival of p-Akt signaling for cell survival. It is concluded that the present study demonstrates the neuro-protective effects of friedelin and glutinol via modulating the capase-3 and PARP-1 expression and modulating the neuronal apoptotic pathways.

In vitro and in vivo characterization of Miconazole Nitrate loaded transethosomes for the treatment of Cutaneous Candidiasis.

This study aimed to fabricate Miconazole Nitrate transethosomes (MCZN TESs) embedded in chitosan-based gel for the topical treatment of Cutaneous Candidiasis. A thin film hydration method was employed to formulate MCZN TESs. The prepared MCZN TESs were optimized and analyzed for their physicochemical properties including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (%EE), Fourier transform infrared spectroscopy (FTIR), Differential scanning calorimetry (DSC), deformability, and Transmission electron microscopy (TEM). In vitro release, skin permeation and deposition, skin irritation, antifungal assay, and in vivo efficacy against infected rats were evaluated. The optimized MCZN TESs showed PS of 224.8 ± 5.1 nm, ZP 21.1 ± 1.10 mV, PDI 0.207 ± 0.009, and % EE 94.12 ± 0.101 % with sustained drug release profile. Moreover, MCZN TESs Gel exhibited desirable pH, spreadability, and viscosity. Notably, the penetration and deposition capabilities of MCZN TESs Gel showed a 4-fold enhancement compared to MCZN TESs. Importantly, in vitro antifungal assay elaborated MCZN TESs Gel anti-fungal activity was 2.38-fold more compared to MCZN Gel. In vivo, studies showed a 1.5 times reduction in the duration of treatment MCZN TESs Gel treated animal group. Therefore, studies demonstrated that MCZN TESs could be a suitable drug delivery system with higher penetration and good antifungal potential.