Development and Evaluation of Methotrexate and Baicalin-Loaded Nanolipid Carriers for Psoriasis Treatment.

Objectives: Psoriasis is a chronic inflammatory, T-lymphocyte immune-mediated skin disease. In this study, skin-permeating nanolipid carriers (NLCs) of Methotrexate (MTX) and Baicalin (BL) were formulated. This further gave formulation of nano-lipid encapsulated carriers for dual-drug delivery of the hydrophilic and hydrophobic drugs through the liposomal gel. Materials and Methods: Optimization of the formulation of NLCs was performed and characterized by determining their particle size, drug permeation, skin irritation, drug loading capacity, stability, in vitro drug release behavior, and in vitro cellular viability. Ex vivo skin permeation and in vivo psoriatic efficiency were also evaluated and compared. Results: Results revealed that the amount of MTX permeating the skin was 2.4 to 4.4 fold greater for dual-drug s than for single NLCs. The optimized dual-drug loaded NLCs had an average particle size (150.20 ± 3.57 nm) and polydispersity index (0.301 ± 0.01) and high entrapment (86.32 ± 2.78% w/w). The MTX nanoparticles exhibit a positive Zeta potential of 38.6 mV. The psoriasis area and severity index scoring showed the lowest skin erythema, skin thickness and scaling. MTX-BL NLCs were inhibited the expression of inflammatory cytokines (tumor necrosis factor-alpha, and interleukin-17) . Conclusion: It can be concluded that newer targeting strategies for NLCs for dual-drug delivery of nano-lipid carriers could be administered topically for the treatment of psoriasis.

Complete Response to Pembrolizumab in Stage IV Alveolar Soft Part Sarcoma After Failure of Four Lines of Treatment: A Case Report and Literature Review.

Alveolar soft part sarcoma (ASPS) is a rare malignant tumor that manifests as a slow-growing soft tissue mass and frequently presents with distant metastasis. The prognosis is variable, and complete remission of metastatic disease has rarely been reported. Our patient was diagnosed with metastatic ASPS at the age of 17, with a primary forearm lesion and metastasis to the lungs. She underwent surgical resection of her forearm mass, followed by adjuvant chemotherapy and radiation to target the lung metastasis. Over the next decade, she had a complicated course of treatment. Her disease continued to slowly progress despite treatment with sunitinib, pazopanib, and a combination of docetaxel and gemcitabine. We eventually treated her with immune checkpoint inhibitors (ICIs). Pembrolizumab, initially in combination with bevacizumab and later as monotherapy, resulted in significant tumor shrinkage, especially in the pulmonary lesions, within the first three months. Subsequent imaging reported complete remission within 15 months and no disease recurrence at her three-year follow-up. Our case highlights one of the very few reported cases of complete remission achieved in metastatic ASPS after treatment with ICIs. ICIs could offer hope for disease remission in advanced ASPS, a rare malignancy that has proven difficult to treat successfully in the past. More studies need to be conducted to further evaluate the efficacy and any associated predictors of successful treatment.

Clinical Presentation, Tumor Characteristics, and Management of Intradiverticular Transitional Cell Carcinoma of the Urinary Bladder: A Systematic Review.

Intradiverticular transitional cell carcinoma (TCC) of the bladder poses unique challenges due to its presentation within the bladder diverticula. This review synthesizes current knowledge on the diagnosis and management of this condition, emphasizing the need for early detection to optimize patient outcomes. The literature underscores the importance of tailored treatment strategies, ranging from radical surgeries to adjuvant chemotherapy, to combat the aggressive nature of intradiverticular TCC. Additionally, stringent post-treatment surveillance protocols are vital in addressing high recurrence rates. Future research directions include biomarker identification, comparative efficacy studies of treatment modalities, and the exploration of innovative therapeutic approaches such as immunotherapy. Longitudinal studies analyzing patient outcomes will provide valuable insights into survival rates and quality of life post-treatment, informing future clinical guidelines. This comprehensive review aims to enhance understanding and management strategies for intradiverticular TCC, paving the way for improved patient care and outcomes in this challenging form of bladder cancer.

Exploring alternative approaches to precision medicine through genomics and artificial intelligence - a systematic review.

The core idea behind precision medicine is to pinpoint the subpopulations that differ from one another in terms of disease risk, drug responsiveness, and treatment outcomes due to differences in biology and other traits. Biomarkers are found through genomic sequencing. Multi-dimensional clinical and biological data are created using these biomarkers. Better analytic methods are needed for these multidimensional data, which can be accomplished by using artificial intelligence (AI). An updated review of 80 latest original publications is presented on four main fronts-preventive medicine, medication development, treatment outcomes, and diagnostic medicine-All these studies effectively illustrated the significance of AI in precision medicine. Artificial intelligence (AI) has revolutionized precision medicine by swiftly analyzing vast amounts of data to provide tailored treatments and predictive diagnostics. Through machine learning algorithms and high-resolution imaging, AI assists in precise diagnoses and early disease detection. AI's ability to decode complex biological factors aids in identifying novel therapeutic targets, allowing personalized interventions and optimizing treatment outcomes. Furthermore, AI accelerates drug discovery by navigating chemical structures and predicting drug-target interactions, expediting the development of life-saving medications. With its unrivaled capacity to comprehend and interpret data, AI stands as an invaluable tool in the pursuit of enhanced patient care and improved health outcomes. It's evident that AI can open a new horizon for precision medicine by translating complex data into actionable information. To get better results in this regard and to fully exploit the great potential of AI, further research is required on this pressing subject.

Current challenges and potential solutions to the use of digital health technologies in evidence generation: a narrative review.

Digital health is a field that aims to improve patient care through the use of technology, such as telemedicine, mobile health, electronic health records, and artificial intelligence. The aim of this review is to examine the challenges and potential solutions for the implementation and evaluation of digital health technologies. Digital tools are used across the world in different settings. In Australia, the Digital Health Translation and Implementation Program (DHTI) emphasizes the importance of involving stakeholders and addressing infrastructure and training issues for healthcare workers. The WHO's Global Task Force on Digital Health for TB aims to address tuberculosis through digital health innovations. Digital tools are also used in mental health care, but their effectiveness must be evaluated during development. Oncology supportive care uses digital tools for cancer patient intervention and surveillance, but evaluating their effectiveness can be challenging. In the COVID and post-COVID era, digital health solutions must be evaluated based on their technological maturity and size of deployment, as well as the quality of data they provide. To safely and effectively use digital healthcare technology, it is essential to prioritize evaluation using complex systems and evidence-based medical frameworks. To address the challenges of digital health implementation, it is important to prioritize ethical research addressing issues of user consent and addressing socioeconomic disparities in access and effectiveness. It is also important to consider the impact of digital health on health outcomes and the cost-effectiveness of service delivery.

Impact of Duration of Catheterization on the Success Rate of Trial Without Catheter in Acute Urinary Retention Due to Benign Prostatic Enlargement.

BACKGROUND: The most common cause of acute urinary retention in men over 50 is benign prostate enlargement (BPE). Following the urethral catheterization, a trial without a catheter (TWOC) under the cover of alpha-blockers is given. The timing of TWOC varies from Day 3 to Day 7 of the retention episode. There is a need to study the improvement in the success rate of TWOC with the increasing number of days of catheterization. OBJECTIVE: To measure the success rate of TWOC in acute urinary retention due to benign prostatic enlargement with increasing days of catheterization. METHOD: The study was conducted in Social Security Teaching Hospital Lahore. Patients who presented with acute urinary retention due to benign prostatic enlargement were catheterized and given alpha-blockers. The patients were divided into two groups, one group having TWOC after three days and the other having TWOC after seven days. The success rate of TWOC was calculated and compared in the two groups. All patients included in the study had the first episode of acute retention with a moderately enlarged prostate and no element of second pathology or neurological deficit. RESULTS: A total of 48 patients were included in the study, divided into two groups of 24 patients each. In the first group who underwent TWOC after seven days of catheterization, 15 out of 24 patients had successful TWOC with a success rate of 62.5%. In the second group of 24 patients, who had TWOC after three days of catheterization, only 11 patients had successful TWOC with a success rate of 45.8%. CONCLUSION: There was a marked improvement in the success rate of TWOC with increasing days of catheterization after an acute retention episode, secondary to BPE.

EI-GC-MS analysis and antidiabetic activity of Pedalium murex seed oil.

The pulverized manifestation of Pedalium murex seeds, excerpted by Soxhlets apparatus after treating with n-hexane. Oil sample was well scrutinized by EI-GC-MS, utilizing the full scan technique within mass ranges lies from 40-700 m/z. 73compounds were recognized among them, 63 compounds were identified and 10 were marked as unidentified (8, 22, 27, 43, 47, 61, 62, 64, 68 and 69). The method was executed by the conventional system of Mass spectroscopy and the data interpreted by considerable match factor ≥95 inspected by NIST library. Antidiabetic activity was carried out by Accu-Chek glucometer. Healthy albino mice were selected to perform antidiabetic activity of seed oil at 100mg/Kg and 200mg/Kg with a standard drug glibenclamide at 5mg/Kg. Antidiabetic activity was observed on 1st, 7th,14th, 21th,27th and 30th days. Statistical calculations and significant outcomes were obtained by One-way and Two-way analysis of variance, followed by Tuckey's test. The phytochemical n-hexadecanoic acid (19.53%) might be responsible for antidiabetic activity of the seed oil.

Simultaneous interaction, degradation, and kinetic study of sparfloxacin with H2 receptor antagonist.

Sparfloxacin is a quinolone carboxylic acid derivative that shows activity as an antimicrobial agent, against a wide range of Gram-negative and Gram-positive organisms. It is clinically useful for the treatment of urinary tract infections, respiratory tract infections and gynecological infections. In this study in vitro drug-drug interaction of sparfloxacin has been carried out with famotidine and ranitidine. For these studies a two-component spectrophotometric process has been developed for sparfloxacin assay in the presence of famotidine or ranitidine. The reproducibility of the method is within ±5%. The technique has been applied to the development of sparfloxacin in methanol. The interaction studies of sparfloxacin with ranitidine and famotidine were carried out in methanol and methanol: Water mixtures (30:70, v/v; 50:50, v/v) and the kinetics of sparfloxacin degradation were evaluated in the presence and absence of famotidine and ranitidine. The decrease in the rate of degradation of sparfloxacin in the presence of famotidine or ranitidine, compared to that of sparfloxacin alone, indicated the possibility of interaction between the sparfloxacin and famotidine or ranitidine. The Thin layer chromatography (TLC) of the degraded solution showed the presence of a degradation product of sparfloxacin. The studies show that complexation with famotidine or ranitidine may affect the bioavailability of sparfloxacin.

Ventilator associated pneumonia in intensive care unit patients: a systematic review.

Ventilator-associated pneumonia (VAP) is the most common ICU acquired pneumonia among patients who are invasively intubated for mechanical ventilation. Patients with VAP suffer an increased mortality risk, financial burden, and length of stay in the hospital. The authors aimed to review the literature to describe the incidence, mortality, and microbiological evidence of VAP. We selected 13 peer-reviewed articles published from 1 January 2010 to 15 September 2022 from electronic databases for studies among adult or pediatric patients diagnosed with VAP expressed per thousand days admitted in the ICU. The VAP rates ranged from 7 to 43 per thousand days, varying among different countries of the world. A significant rate of mortality was observed in 13 studies ranging from 6.3 to 66.9%. Gram-negative organisms like Acinetobacter spp., Pseudomonas aeruginosa Gram-positive organisms like Staphylococcus aureus were frequently found. Our findings suggest an alarming situation of VAP among patients admitted to the intensive care units with increasing incidence and mortality. The review also found that VAP is more common in males and that there is a significant variation in the incidence and mortality rates of VAP among different countries. The findings of this review can inform the development of infection control and prevention strategies to reduce the burden of VAP. Thus, there is a crucial need for control and preventive measures like interventional studies and educational programs on staff training, hand-hygiene, and the appropriate use of ventilator bundle approach to curb this preventable threat that is increasing at an alarming rate.

Comprehensive targeted treatment options available for Breast cancer stem cells; A literature review of the last 10 years' developments.

Breast Cancer Stem Cells (BCSCs), unlike normal breast cells, exhibit the potential for self-regeneration and tumour formation and express unique markers. Studies have highlighted their role in tumour progression, recurrence, and treatment resistance. BCSCs can be one of the reasons that resistance is encountered despite recent advances in the treatment of breast cancer (BC). This review underlines the clinical implications at the molecular level of different cellular pathways, cellular level interactions in Tumour Micro Environment (TME), and types of markers and receptors involved in tumorigenesis. It accentuates the importance of comprehensive targeted treatment options available for BCSCs so that targeted modalities can be introduced to deal with treatment resistance. Stem cells (SCs) are a developing field, and limited data is available from our country to use stem cell-targeted treatment plans as a therapeutic option. Therefore, this literature review will provide insight for future research in this domain.

The RIPASA scoring system: A new Era in appendicitis diagnosis.

Introduction: Even though acute appendicitis is a common acute abdominal disease, it is nonetheless difficult to detect. In order to minimize the risk of complications and negative exploratory procedures, early and accurate diagnosis is critical.We aimed to compare the predictive accuracy of the RIPASA score in diagnosing acute appendicitis with the gold standard of histopathological proven appendicitis as the gold standard. Methodology: A Prospective Cohort Study was conducted from December 2021 to May 2022 at KRL Hospital. A total of 171 patients who sought treatment for acute RIF pain or suspected appendicitis were included in the study. Patients' surgical proclivities were judged in part based on images and surgeon's expertise. SPSS version 26 was used to enter and analyze the data. This was done using a chi-square test and a Kendall's Tau (Kendall Rank Correlation Coefficient) to evaluate both groups of patients. Results: At diagnosis, the mean age was 37.93 10.36 years. Kendall's Tau and Chi Square were shown to be significant in contrast to Alvarado scoring. RIPASA Scoring exhibited a 98.02% positive predictive value, a 96.75% sensitivity, an 82.35% specificity, and 95.3% diagnostic accuracy. Conclusion: The RIPASA score is superior to the Alvarado score when it comes to detecting acute appendicitis in Asian populations. With a brief medical history, a clinical examination, and two simple procedures, parameters can be simply and swiftly obtained in any demographic circumstance.

Role of Mushroom as Dietary Supplement on Performance of Poultry.

The objective of this review is to summarize the effect of commonly used mushrooms (particularly Pleurotus ostreatus or oyster mushroom, Agaricus bisporus or Button mushroom, Lentimula edodes or shiitake mushroom, and Ganoderma lucidum or reishi mushroom) in poultry diets on performance of broilers and layers. It can be concluded from different studies that mushrooms and their polysaccharides can play important roles in poultry production: (1) Polysaccharides in mushrooms may act as immune enhancers or immunomodulators and show antibacterial, antiviral, antiparasitic bioactivities; (2) phenolic compounds of mushrooms may act as antioxidants; (3) mushrooms in broiler's diet may be used as growth promoters as an alternative to antibiotics; (4) mushrooms in the diet may improve egg production and quality; (5) mushrooms may be used as a safe and effective alternative for inducing molt, enhancing immunity, reducing Salmonella growth, and returning to egg production. Further studies are needed to investigate the effects of mushrooms to improve productive performance in chickens and to illuminate the possible modes of action related to the gut ecosystem and the immune response.

Effects of black cumin seed (Nigella sativa L.) on performance and immune system in newly evolved crossbred laying hens.

BACKGROUND: A limited number of studies have tested the effect of diets supplemented with black cumin seed (BCS) on the performance of laying hen. OBJECTIVE: To determine the effects of various levels of dietary BCS on the performance of laying hen. BIRDS AND METHODS: Three hundred 40-week-old rural Leghorn (White Leghorn males X F1 females of Fayoumi male X Rhode Island Red female) crossbred hens were randomly assigned to four groups with five replicates of 15 birds each (75 laying hens per group), and fed diets supplemented with 0%, 3%, 4% or 5% BCS for 60 days. Statistical analysis was performed by means of ANOVA. RESULTS: BCS at all levels revealed greater egg production, egg weight and egg mass than the control group. Similarly, feed conversion was improved by 0.50, 0.55 and 0.36 points compared to controls with the addition of 3%, 4% or 5% levels of BCS, respectively. Haugh units and yolk weights of eggs from hens that were fed diets containing 3%, 4% and 5% BCS were significantly greater than those from the control group. Supplementation of 4% or 5% BCS significantly increased shell thickness and decreased serum LDL cholesterol and egg yolk cholesterol concentration as compared to other groups. Mean hemagglutination inhibition titers against Newcastle disease virus were higher than in controls. CONCLUSION: BCS at levels of 4% or 5% positively influenced egg production, egg weight and shell quality. Furthermore, it decreased the concentration of serum LDL cholesterol and egg yolk cholesterol concentrations and enhanced immunity against Newcastle disease virus.

Availability of expanded programme of immunization services provided to children in a rural Pakistani village.

OBJECTIVES: To evaluate the immunization status of children under 5 years age, living in the Nurpur Shahan area and to identify various factors which influenced the rate of immunization. METHODS: A cross sectional study was conducted in which mothers of children under 5 years of age were questioned about the immunization of their children and the immunization services provided in the area. Systematic random sampling was used and the collected data was analyzed using SPSS v. 10.0. RESULTS: The overall immunization rate in the children of Nurpur Shahan was 77.4%. This study found strong correlations to immunization rates in children. Increased educational status of the mother, greater maternal immunization during pregnancy, and home delivery of vaccines, were all directly linked to higher rates of immunization amongst children. Lack of awareness, followed by inadequate facilities were the most commonly cited reasons for discontinuing the programme or abstaining from it altogether. CONCLUSION: The EPI coverage in Nurpur Shahan is quite well established, but still left room for improvement. Factors that encouraged higher immunization rates were more educated mothers, better awareness and availability of door-to-door services.

Kinetics of batch single cell protein production from rice polishings with Candida utilis in continuously aerated tank reactors.

Single cell protein was produced from the defatted rice polishings by fermentation with Candida utilis in an aerated 14-L fermentor to optimize bioprocess variables. Maximum values of specific growth rate coefficient (mu, h(-1)), cell mass yield (Y(X/S), g/g) and cell mass productivity (g/Lh) were 0.31, 0.65, and 1.24, respectively under optimized conditions of aeration rate (1 v.v(-1) m(-1)), dissolved oxygen (50%), corn steep liquor (5%), temperature (35 degrees C), and substrate concentration (90 g rice polishings/L) in yeast salt medium (pH 6.0). The kinetic parameters for 50-L fermentor under same conditions were 0.33 h(-1), 0.66 g/g, 1.33 g/Lh, 2.25 g/Lh, 1.23 g/Lh, 0.45 g/g substrate and 0.20 g/g cell h for mu, Y(X/S), Q(X), Q(S), Q(CP), Y(TP/S), and q(CP), respectively and were significantly higher than their respective values reported on C. utilis in batch culture studies. This biomass protein contained 23.6%, 32.75%, 11.50%, 12.95%, 10.5%, and 0.275% true protein, crude protein, crude fiber, ash, cellulose and RNA content respectively. This implied that the fermentation process could be up scaled to manufacture animal feed. Gross metabolizable energy content of dried SCP was 29,711 kcal/kg and indicated that the SCP could serve both as energy as well as a protein source. Yeast can replace expensive feed ingredients currently being incorporated in poultry feed and can reduce cost of poultry ration by 0.33 US dollars-0.51 US dollars/100 kg bag and improve the economics of feed production in our country.