Evaluation of clinical and laboratory characteristics of dengue viral infection and risk factors of dengue hemorrhagic fever: a multi-center retrospective analysis.

BACKGROUND: Dengue Viral Infection (DVI) has become endemic in Pakistan since the first major outbreak in Karachi in 1996. Despite aggressive measures taken by relevant authorities, Pakistan has been dealing with a worsening dengue crisis for the past two decades. DHF is severe form of dengue infection which is linked with significant morbidity and mortality. Early identification of severe dengue infections can reduce the morbidity and mortality. In this context we planned current study in which we find out the different factors related with DHF as well as clinical laboratory features of DHF and compare them to DF so that patients can be best evaluated for DHF and managed accordingly at admission. METHODS: Retrospective study conducted over a period of 6 years (2013-2018) in two tertiary care hospitals in Pakistan. Data were collected by using a pre-structured data collection form. Data were statistically analyzed to determine the clinical and laboratory characteristics of DVI and risk factors of dengue hemorrhagic fever (DHF). RESULTS: A total 512 dengue cases (34.05 ± 15.08 years; Male 69.53%) were reviewed. Most common clinical manifestations of DVI were fever (99.60%), headache (89.1%), chills (86.5%), rigors (86.5%), myalgia (72.3%). Less common clinical manifestations were vomiting (52.5%), arthralgia (50.2%) and skin rashes (47.5%). Furthermore, nasal bleeding (44.1%), gum bleeding (32.6%), pleural effusion (13.9%) and hematuria (13.1%) were more profound clinical presentations among DHF patients. Mortality rate was 1.5% in this study. Logistic regression analysis indicated that delayed hospitalization (OR: 2.30) and diabetes mellitus (OR:2.71), shortness of breath (OR:2.21), association with risk groups i.e., living near stagnant water, travelling to endemic areas, living in endemic regions (OR:1.95), and presence of warning signs (OR:2.18) were identified as risk factors of DHF. Statistically we found that there is strong association of diabetes mellitus (DM) with DHF while the patient suffering from DM individually had higher odds (2.71) of developing DHF than patients without disease. CONCLUSIONS: The current study demonstrated that the clinical and laboratory profiles of DF and DHF are significantly distinct. Significant predictors of DHF were advanced age, diabetes mellitus, ascites, pleural effusion, thick gallbladder and delayed hospitalization. The identification of these factors at early stage provides opportunities for the clinicians to identify high risk patients and to reduce dengue-related morbidity and mortality.

Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

Quercetin in semen extender improves frozen-thawed spermatozoa quality and in-vivo fertility in crossbred Kamori goats.

This study investigated the antioxidant effect of quercetin-treated semen on frozen-thawed spermatozoa quality and in-vivo fertility in crossbred Kamori goats. In total, 32 ejaculates from four fertile bucks were diluted in Tris-based egg yolk extender with varying levels of quercetin (0, 1, 5, 10, and 15 µM). Qualified semen samples were pooled and frozen in French straws. The results revealed that the addition of quercetin in the semen extender increased (p < 0.05) frozen-thawed sperm total motility (TM), progressive motility (PM), rapid velocity (RV), average path velocity (VAP), straight line velocity (VSL), curvilinear velocity (VCL), and amplitude of lateral head (ALH) displacement in contrast to the control group. Quercetin supplementation had no effect on beat cross frequency (BCF), straightness (STR), and linearity (LIN) (p > 0.05). Quercetin showed significantly higher (p < 0.05) plasma membrane and acrosome integrity and viability (p < 0.05) of spermatozoa in contrast to the control group. Quercetin in the semen extender significantly increased (p < 0.05) superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), ascorbate peroxidase (APX), and total antioxidant capacity (TAC) levels while reduced (p < 0.05) the contents of total oxidant status (TOS) and malondialdehyde (MDA), which were in contrast to the control group. Ultrasound results revealed that 24 out of 30 (80%) goats were found pregnant when semen was treated with 5 µM quercetin while the control group showed 18 out of 30 (60%) animals were pregnant. Thus, the study concluded that 5 µM quercetin-treated semen was found to be efficient, showed increased antioxidant status, and reduced oxidant production, leading to improved spermatozoa quality and in-vivo fertility in goats.

Artificial neural network-assisted prediction of radiobiological indices in head and neck cancer.

Background and purpose: We proposed an artificial neural network model to predict radiobiological parameters for the head and neck squamous cell carcinoma patients treated with radiation therapy. The model uses the tumor specification, demographics, and radiation dose distribution to predict the tumor control probability and the normal tissue complications probability. These indices are crucial for the assessment and clinical management of cancer patients during treatment planning. Methods: Two publicly available datasets of 31 and 215 head and neck squamous cell carcinoma patients treated with conformal radiation therapy were selected. The demographics, tumor specifications, and radiation therapy treatment parameters were extracted from the datasets used as inputs for the training of perceptron. Radiobiological indices are calculated by open-source software using dosevolume histograms from radiation therapy treatment plans. Those indices were used as output in the training of a single-layer neural network. The distribution of data used for training, validation, and testing purposes was 70, 15, and 15%, respectively. Results: The best performance of the neural network was noted at epoch number 32 with the mean squared error of 0.0465. The accuracy of the prediction of radiobiological indices by the artificial neural network in training, validation, and test phases were determined to be 0.89, 0.87, and 0.82, respectively. We also found that the percentage volume of parotid inside the planning target volume is the significant parameter for the prediction of normal tissue complications probability. Conclusion: We believe that the model has significant potential to predict radiobiological indices and help clinicians in treatment plan evaluation and treatment management of head and neck squamous cell carcinoma patients.

Successful use of a patient specific 3D-printed biomodel as surgical guide for excision of juvenile nasopharyngeal angiofibroma extending to skull base: A case report.

Background: 3-Dimensional (3D) printing has proven its role in various fields. Recently, 3D printing has also been introduced in the otolaryngology domain. The nasopharynx, paranasal sinuses, and the anterior skull base have a complex anatomy. Critical structures must be delicately protected and preserved during a surgical procedure. It is, therefore, very important for the surgeon to have an excellent spatial understanding of the complex surgical field that is being traversed. Case Description: Our case is of a 19-year-old male with a 2-month history of recurrent epistaxis, nasal blockage, and headache. Based on the computed tomography scan and the clinical presentation, the patient was diagnosed with juvenile nasopharyngeal angiofibroma. The patient underwent angioembolization of the tumor followed by endoscopic surgical resection. The patient remained stable postoperatively and demonstrated a good recovery in the follow-up visit with no signs of cranial deficits. This case report highlights the use of a patient-specific 3D-printed biomodel to visualize this rare tumor of the nasopharynx. The benefits of using the model in surgical planning, patient education, and resident training are reported. We found that the ability to visualize the tumor on a tangible model, viewing its actual size in relation to the adjacent anatomy and all the structures associated with it, greatly enhances the surgeon's capacity to tackle such a difficult tumor endoscopically. Conclusion: Incorporating 3D-printed biomodels in surgical practice should result in improved outcomes for the patients.

Structural, morphological, mechanical, and electronic properties of nickel substituted manganese oxide (NixMn1-xO, x= 0.0, 0.2, 0.4) for electronic applications.

The structural, morphological, mechanical, and electronic properties of nickel-substituted manganese oxide (NixMn1-xO, where x = 0.0, 0.2, and 0.4) were studied using experimental techniques. The compounds were synthesized using a hydrothermal method. The face-centered cubic structures of the examined compounds were confirmed by XRD. Scanning electron microscopy (SEM) images revealed that the particles were well-shaped, while elemental mapping with energy dispersive spectroscopy (EDS) confirmed that the examined compounds had the appropriate proportions of Ni, Mn, and O. The FT-IR spectroscopy results indicated the respective functional groups. Raman spectroscopy results disclosed the vibration modes of the respective materials. The Tauc plot reveals the semiconducting nature of the compounds. The UV-Vis bandgap study revealed the semiconductor natures of compounds. This demonstrates that these nanoparticles can be used in atom lasers, photovoltaics, and other electronic applications.

Comparison of EKFC, Pakistani CKD-EPI and 2021 Race-Free CKD-EPI creatinine equations in South Asian CKD population: A study from Pakistani CKD community cohort.

INTRODUCTION: South Asian individuals possess a high risk of chronic kidney disease. There is a need to study, evaluate, and compare the newly suggested glomerular filtration rate (eGFR) equations for accurate CKD diagnosis, staging, and drug dosing. This study aimed to (1) evaluate the European Kidney Function Consortium (EKFC), Pakistani CKD-EPI, and 2021 Race-Free CKD-EPI creatinine equation in the South Asian population with CKD and (2) to examine the expected implications on both CKD classification as well as End Stage Renal Disease (ESRD) prevalence across these equations in South Asian population. METHODS: We carried out a cross-sectional investigation on 385 participants, a CKD cohort ≥ 18 years, at Allama Iqbal Medical College, Jinnah Hospital, Lahore. Serum creatinine was measured by Jaffe's method and rGFR was measured by inulin clearance. RESULTS: Pakistani CKD-EPI has a lower median difference at -1.33 ml/min/1.73m2 elevated precision (IQR) at 2.33 (-2.36, -0.03) and higher P30 value at 89.35% than 2021 CKD-EPI and EKFC equations. The mean difference (ml/min/1.73m2), 95% agreement limits (ml/min/1.73m2) of CKD-EPI PK: -1.18, -6.14, 2021 CKD-EPI: -5.98, -13.24 and EKFC: -5.62, -13.01 (P <0.001). These equations highly correlated to rGFR (P <0.001). An upward re-classification in GFR categories was shown by 2021 CKD-EPI and EKFC compared to the Pakistani CKD-EPI equation. However, there was an exception regarding the G5 category, where an elevated count of 217 (56.36%) was shown for CKD-EPI PK. The prevalence of ESRD was seen in entire age groups and prevailed among females more than in males overall equations. CONCLUSIONS: Pakistani CKD-EPI exhibited outstanding performance, while 2021 CKD-EPI and EKFC demonstrated poor performances and could not show an adequate advantage for both CKD classification and prevalence of ESRD compared to Pakistani CKD-EPI. Therefore, Pakistani CKD-EPI appears optimal for this region and warrants future validation in other South Asian countries. In contrast, suitable measures must be implemented in Pakistani laboratories.

Flow control by circular cavities in lateral flow porous membranes.

This research explores the flow penetration in porous media by virtue of capillary action and geometric control of the liquid imbibition rate in microfluidic paper-based analytical devices (µPADs) having applications in food quality management, medical diagnostics, and environmental monitoring. We examine changes in flow resistance and membrane geometry, aiming to understand factors influencing capillary penetration rates for various practical applications. We conducted experiments and simulations using lateral porous membranes and altered the flow resistance by changing the liquids or the paper channel geometry by adding cavities. From experiments, it was revealed that by creating a circular cavity in the paper channel, the penetration rate was sufficiently altered. Moreover, increasing the cavity size and type of liquid (w.r.t. viscosity) also caused a decrease in the flow rate. Imbibition rates were also influenced by the position of the cavities in the paper channel. The maximum delay for water was almost 2 times with a 16 mm circular cavity located at 3 cm from strip bottom edge. Overall, we attained a maximum delay in the case of castor oil which was almost 85 times slower than water and 3.7 times slower than olive oil. A good agreement was observed with CFD analysis. We believe that this research would help in developing advance techniques to enhance the flow control strategies in µPADs and indicators.

Preparation and Evaluation of a Self-Emulsifying Drug Delivery System for Improving the Solubility and Permeability of Ticagrelor.

Ticagrelor (TCG) is a BCS class IV antiplatelet drug used to prevent platelet aggregation in patients with acute coronary syndrome, having poor solubility and permeability. The goal of this study was to develop a self-nanoemulsifying drug delivery system (SNEDDS) of TCG to improve its solubility and permeability. The excipients were selected based on the maximum solubility of TCG and observed by UV spectrophotometer. Different combinations of oil, surfactant, and co-surfactant (1:1, 2:1, and 3:1) were used to prepare TCG-SNEDDS formulations, and pseudo-ternary phase diagrams were plotted. The nanoemulsion region was observed. Clove oil (10-20%), Tween-80 (45-70%), and PEG-400 (20-45%) were used as an oil, surfactant, and co-surfactant, respectively. The selected formulations (F1, F2, F3, F4, F5, and F6) were analyzed for ζ potential, polydispersity index (PDI), ζ size, self-emulsification test, cloud point determination, thermodynamic studies, entrapment efficiency, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), in vitro dissolution, ex vivo permeation, and pharmacodynamic study. The TCG-SNEDDS formulations exhibited ζ potential from -9.92 to -6.23 mV, a ζ average of 11.85-260.4 nm, and good PDI. The in vitro drug release in phosphate buffer pH 6.8 from selected TCG-SNEDDS F4 was about 98.45%, and F6 was about 97.86%, displaying improved dissolution of TCG in 0.1 N HCl and phosphate buffer pH 6.8, in comparison to 28.05% of pure TCG suspension after 12 h. While the in vitro drug release in 0.1 N HCl from F4 was about 62.03%, F6 was about 73.57%, which is higher than 10.35% of the pure TCG suspension. In ex vivo permeability studies, F4 also exhibited an improved apparent permeability of 2.7 × 10-6versus 0.6708 × 10-6 cm2/s of pure drug suspension. The pharmacodynamic study in rabbits demonstrated enhanced antiplatelet activity from TCG-SNEDDS F4 compared to that from pure TCG suspension. These outcomes imply that the TCG-SNEDDS may serve as an effective means of enhancing TCG's antiplatelet activity by improving the solubility and permeability of TCG.

Genotypic analysis of hepatitis E virus (HEV) from sporadic symptomatic cases in Pakistan.

Pakistan is the fifth most populous nation in the world and faces several challenges, including devastating floods, sub-optimal sanitary conditions, clustered accommodations, and unregulated cross-border movements. These drastic population shifts make it vulnerable to the efficient spread of the Hepatitis E virus (HEV). The current study analyzed the genotypic characteristics and variants of the Hepatitis E virus circulating in the population of Pakistan. A total of 75 ELISA-IgM positive samples were collected from three metropolitan cities: Lahore, Peshawar, and Karachi, and subjected to viral RNA extraction. The amplification of the HEV RNA-dependent RNA polymerase (RdRp) region was done using Nested PCR and degenerate primers. Out of the total, 40% of the samples were positive for HEV RNA. Sequencing and phylogenetic analysis identified the new HEV isolates as Subtype 1 g, a subtype within an existing HEV genotype 1. This shift warrants investigation into its impact on clinical manifestation and disease severity. Importantly, this study marks the first HEV subtype analysis in Pakistan, contributing valuable insights into subtype diversity and prevalence in the region.

Response Surface Methodology (RSM) approach to formulate and optimize the bilayer combination tablet of Tamsulosin and Finasteride.

An orally administered bilayer tablet with Tamsulosin (TAM) as the sustained release (SR) and Finasteride (FIN) as immediate release (IR) was manufactured. A response surface methodology was employed to formulate bilayer tablets with individual release layers, i.e., sustained and immediate release (SR and IR). Independent variables selected in both cases comprise hydroxypropyl methylcellulose (HPMC) as SR polymer, and avicel PH102 in the inner layer while Triacetin and talc in the outer layer, respectively. Tablets were prepared by direct compression, a total of 11 formulations were prepared for inner layer TAM, and 9 formulations for outer layer FIN were designed; these formulations were evaluated for hardness, friability, thickness, %drug content, and %drug release. A central composite design was employed in response surface methodology to design and optimize the formulation. The percentage of drug released was evaluated by in-vitro USP dissolution method of optimized formulation for 0.5, 2, and 6 hrs, and results were 24.63, 52.96, and 97.68 %, respectively. Drug release data was plotted in various kinetic models using a D.D solver, where drug release was first order that is concentration dependent and was best explained by Korsmeyer-Peppa kinetics, as the highest linearity was observed (R2 = 0.9693). However, a very close relationship was also noted with Higuchi kinetics (R2 = 0.9358). The mechanism of drug release was determined through the Korsmeyer model, and exponent "n" was found to be 0.4, indicative of an anomalous diffusion mechanism or diffusion coupled with erosion.

Atypical Complications during the Course of COVID-19: A Comprehensive Review.

COVID-19 is primarily a respiratory disease, but numerous studies have indicated the involvement of various organ systems during the course of illness. We conducted a comprehensive review of atypical complications of COVID-19 with their incidence range (IR) and their impact on hospitalization and mortality rates. We identified 97 studies, including 55 research articles and 42 case studies. We reviewed four major body organ systems for various types of atypical complications: (i) Gastro-intestinal (GI) and hepatobiliary system, e.g., bowel ischemia/infarction (IR: 1.49-83.87%), GI bleeding/hemorrhage (IR: 0.47-10.6%), hepatic ischemia (IR: 1.0-7.4%); (ii) Neurological system, e.g., acute ischemic stroke/cerebral venous sinus thrombosis/cerebral hemorrhage (IR: 0.5-90.9%), anosmia (IR: 4.9-79.6%), dysgeusia (IR: 2.8-83.38%), encephalopathy/encephalitis with or without fever and hypoxia (IR: 0.19-35.2%); (iii) Renal system, e.g., acute kidney injury (AKI)/acute renal failure (IR: 0.5-68.8%); (iv) Cardiovascular system, e.g., acute cardiac injury/non-coronary myocardial injury (IR: 7.2-55.56%), arrhythmia/ventricular tachycardia/ventricular fibrillation (IR: 5.9-16.7%), and coagulopathy/venous thromboembolism (IR: 19-34.4%). This review encourages and informs healthcare practitioners to keenly monitor COVID-19 survivors for these atypical complications in all major organ systems and not only treat the respiratory symptoms of patients. Post-COVID effects should be monitored, and follow-up of patients should be performed on a regular basis to check for long-term complications.

Development and immunological evaluation of an mRNA-based vaccine targeting Naegleria fowleri for the treatment of primary amoebic meningoencephalitis.

More than 95% of patients fall victim to primary amoebic meningoencephalitis (PAM), a fatal disease attacking the central nervous system. Naegleria fowleri, a brain-eating microorganism, is PAM's most well-known pathogenic ameboflagellate. Despite the use of antibiotics, the fatality rate continues to rise as no clinical trials have been conducted against this disease. To address this, we mined the UniProt database for pathogenic proteins and selected assumed epitopes to create an mRNA-based vaccine. We identified thirty B-cell and T-cell epitopes for the vaccine candidate. These epitopes, secretion boosters, subcellular trafficking structures, and linkers were used to construct the vaccine candidate. Through predictive modeling and confirmation via the Ramachandran plot (with a quality factor of 92.22), we assessed secondary and 3D structures. The adjuvant RpfE was incorporated to enhance the vaccine construct's immunogenicity (GRAVY index: 0.394, instability index: 38.99, antigenicity: 0.8). The theoretical model of immunological simulations indicated favorable responses from both innate and adaptive immune cells, with memory cells expected to remain active for up to 350 days post-vaccination, while the antigen was eliminated from the body within 24 h. Notably, strong interactions were observed between the vaccine construct and TLR-4 (- 11.9 kcal/mol) and TLR-3 (- 18.2 kcal/mol).

Research progress in the role and mechanism of Leucine in regulating animal growth and development.

Leucine, a branched-chain amino acid, is essential in regulating animal growth and development. Recent research has uncovered the mechanisms underlying Leucine's anabolic effects on muscle and other tissues, including its ability to stimulate protein synthesis by activating the mTORC1 signaling pathway. The co-ingestion of carbohydrates and essential amino acids enhances Leucine's anabolic effects. Moreover, Leucine has been shown to benefit lipid metabolism, and insulin sensitivity, making it a promising strategy for preventing and treating metabolic diseases, including type 2 diabetes and obesity. While emerging evidence indicates that epigenetic mechanisms may mediate Leucine's effects on growth and development, more research is needed to elucidate its mechanisms of action fully. Specific studies have demonstrated that Leucine promotes muscle growth and metabolic health in animals and humans, making it a promising therapeutic agent. However, it is essential to note that Leucine supplementation may cause digestive issues or interact with certain medications, and More study is required to determine definitively optimal dosages. Therefore, it is important to understand how Leucine interacts with other nutrients, dietary factors, and lifestyle habits to maximize its benefits. Overall, Leucine's importance in human nutrition is far-reaching, and its potential to prevent muscle loss and enhance athletic performance warrants further investigation.

Embolization of arteriovenous malformations of head and neck: A systematic review.

BACKGROUND: Cervicofacial arteriovenous malformations (AVMs) are a significant source of morbidity. Endovascular embolization has emerged as a promising treatment technique for these lesions. However, current literature on cervicofacial AVM embolization mostly consists of single-agent oriented case series, and to date, no comprehensive study has compared the outcomes of available embolic agents. PURPOSE: To investigate the performance of different embolic agents in the management of cervicofacial AVMs. METHODS: We systematically searched Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials Scopus, and Web of Science. Studies providing data for the endovascular treatment of cervicofacial AVMs were included. The data regarding complication and cure rates were collected for each embolic agent. Pooled event rates were presented as descriptive statistics. RESULTS: Eleven studies comprising 204 patients were included in the review. The overall complete and partial cure rates were 62.2% (127/204) and 36.2% (74/204), respectively. Embolization failed to achieve significant improvement in only 1.6% (3/204) of the patients. The complete cure rates were 87.5% (75-100%) for n-Butyl cyanoacrylate (NBCA, glue), 80.5% (61-100%) for Onyx (Medtronic, MN, USA), and 51.5% (18-85%) for ethanol. The overall complication rate was 30% (61/204). The complication rates were 33% (12.5-53%) for ethanol, 14% (0-28%) for Onyx, and 0% for NBCA. CONCLUSIONS: Our systematic review supports that endovascular embolization is an effective treatment option for cervicofacial AVMs. In our review, the use of Onyx and NBCA was associated with consistently high complete cure rates and a promising safety profile. However, more research is needed to investigate the use of different embolic agents in the treatment of cervicofacial AVMs.