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Abstract Adoption of a health information system is always a challenge for hospitals. It is because most of the medical staff do not have enough skills to use the new technology and due to the sensitivity of medical data. These factors pose a challenge for the successful adoption of health information system in hospitals. The aim of this research is to find out the factors which influence the adoption of information systems in hospitals. The study investigated the impact of the Financial status of the Hospital; Perceived Usefulness and Perceived Ease of Use on the adoption of health information systems through a questionnaire survey. Data was collected from 602 healthcare workers from 20 hospitals through close-ended questionnaire in Pakistan, where the adoption of health information systems is very slow. PLS-SEM was used for the analysis. The findings show that the Financial status of the Hospital; Perceived Usefulness and Perceived Ease of Use have positive and significant role in the adoption of Health Information Systems. The finding also shows that hospital size moderates the relationship of Perceived ease of use and the adoption of health information systems and interestingly it does not moderate the relationship among perceived usefulness and financial strength toward the adoption of health information systems. The study concludes that perceived ease of use, perceived usefulness and financial strength are the main factors, necessary for the adoption of health information systems. The findings of the study have useful implications for policy makers, medical professionals to successfully adopt health information systems in hospitals. It also provides new avenues for researchers to explore other factors and test this framework in other countries.

Accurate evapotranspiration (ET) estimation is crucial for sustainable water management in the diverse and water-scarce Mediterranean region. This study compares three prominent models (Simulator of Terrestrial Ecohydrological Processes and Systems (STEPS), Soil-Canopy-Observation of Photosynthesis and Energy fluxes (SCOPE), and Two-Source Energy Balance (TSEB)) with established global datasets (Moderate Resolution Imaging Spectroradiometer 8-day global terrestrial product (MOD16A2), Global Land Evaporation Amsterdam Model (GLEAM), and TerraClimate) at multiple spatial and temporal scales and validates model outcomes with eddy covariance based ground measurements. Insufficient ground-based observations limit comprehensive model validation in the eastern Mediterranean part (Turkey and Balkans). The results reveal significant discrepancies among models and datasets, highlighting the challenges of capturing ET variability in this complex region. Differences are attributed to variations in ecosystem type, energy balance calculations, and water availability constraints. Ground validation shows that STEPS performs well in some French and Italian forests and crops sites but struggles with seasonal ET patterns in some locations. SCOPE mostly overestimates ET due to detailed radiation flux calculations and lacks accurate water limitation representation. TSEB faces challenges in capturing ET variations across different ecosystems at a coarser 10 km resolution. No single model and global dataset accurately represent ET across the entire region. Model performance varies by region and ecosystem. As GLEAM and TSEB excel in semi-arid Savannahs, STEPS and SCOPE are better in grasslands, croplands, and forests in few locations (5 out of 18 sites) which indicates these models need calibration for other locations and ecosystem types. Thus, a region-specific model calibration and validation, sensitive to extremely humid and arid conditions can improve ET estimation across the diverse Mediterranean region.

MicroRNAs (miRNAs) are small non-coding molecules that play a pivotal part in brain development and the processes of establishment and maintenance of dendrites and neurite outgrowth by modulating gene expression. Dysregulation of miRNAs has been linked with neurological disorders. Exogenous miRNAs are unstable in the plasma due to degradation by nucleases; hence, choosing a harmless and effective delivery mode is crucial in the quest for miRNA-based therapeutics to treat neurological disorders. This review aims to shed light on the emerging role of nanotechnology-based approaches using miRNAs to treat neurodegenerative disorders. Nanotechnology encompasses a broad spectrum of applications, one of which is its role in developing nanoscale drug delivery systems. Nanotechnology-based drug delivery systems have attracted the attention of researchers due to the superiority of this mode over conventional treatment systems in terms of their favorable attributes such as bio-compatibility, bio-degradability, extremely small size, and the ability to cross the blood-brain barrier. This review explores nanotechnology-based approaches using miRNAs highlighting the use of viral vectors as well as non-viral vectors (such as exosomes, liposome nanoparticles, gold and magnetic nanoparticles, dendrimer-based nanoparticles, polymeric nanoparticles) to treat neurodegenerative disorders.

Leukemoid Reaction (LR) signifies leukocytosis characterized by mature neutrophils. The incidence of LR is about 1 % among hospitalized patients. Mucormycosis is a rare, aggressive, fatal fungal infection that afflicts immune-compromised patients. This study discusses the case of concomitant leukemoid reaction and mucormycosis in a patient with severe COVID-19 infection.

Background: Effective contraceptive methods are necessary to control the exploding population of India for its socioeconomic development. Postpartum intra uterine contraceptive device (PPIUCD) has a huge potential as an effective contraceptive method. The increased institutional deliveries provide women an easy access to immediate PPIUCD services. Aim: To study acceptability rate of postpartum intrauterine contraceptive device among women attending government general hospital, Guntur. Materials and methods: This was a prospective observational study conducted in the department of Obstetrics and Gynaecology, Government General Hospital, Guntur, for a period of 6 months between 1st October 2020 to 31st March 2021. Subjects were antenatal women more than 34 weeks gestational age and women in their immediate postpartum period. 300 subjects were counseled regarding PPIUCD. Using validated questionnaire including age, education, parity, awareness of PPIUCD, willingness or refusal and reasons for willingness or refusal of PPIUCD were collected and data recorded. Acceptability was defined as the number of women who agreed and got PPIUCD inserted. Results: Out of 300 subjects counseled only 96 accepted PPIUCD insertion. Acceptability rate was found to be 32%. Acceptance was more in booked subjects (44.44%) and in subjects with prior knowledge of PPIUCD (80%). Husband’s refusal was the reason for refusal in 54.9%. Conclusion: Acceptability of PPIUCD was very poor in spite of PPIUCD being safe, effective and long acting with very few side effects. Proper counseling and awareness programs can increase acceptability of PPIUCD.

Background. The treatment of peripheral diabetic neuropathy is difficult to treat considering the pain is severe, long-lasting and does not respond to analgesics. Gabapentin has been recommended as the first line treatment for DPN but owing to cognitive dysfunction and other side effects the drug is discontinued. Recent studies suggest that oxcarbazepine; an antiepileptic drug has good-efficacy in management of DPN. This prospective, observational and comparative study was done to compare gabapentin and oxcarbazepine monotherapy in patient of DPN. Objectives. We assessed the efficacy of Oxcarbazepine monotherapy in terms of pain score, sleep score and quality of life and compared with gabapentin monotherapy. Methods. 100 patients with DPN or examinations suggesting DPN were divided into 2 groups to receive gabapentin 300- 1200 mg/day or Oxcarbazepine 300-600mg/day. Assessment of pain scores, sleep score and quality of life were done at different duration during the course of therapy. Results. Out of total subject selected, the maximum (46%) subjects were between age group 60-90 years and the least effected were (24%) between age group 50-59 years. Male were more prevalent with 57% when compared to females with 43%. Improvement in Sleep was seen on using Group II with p value (0.0005). However, the correlation of Pain and Quality of life with the treatment shows p –value 0.24, 0.31 and 0.27 respectively showing non-significance. Conclusion. The sleep improved statistically correlated in patients with DPN, but not with quality of life and pain as the calculated p value was (p= 0.24, 0.31 and 0.27) respectively. Findings of this study suggest that oxcarbazepine can be used as an alternative treatment owing to its similar analgesic efficacy and improvement in sleep.

Aims: In a cross-sectional study we aimed to assess the correlation between ultrasound transient elastography (TE), serum ferritin (SF), liver iron content (LIC) by magnetic resonance imaging (MRI) T2* along with the fibrosis-4 (FIB-4) score as a screening tool to detect significant liver fibrosis among chronically transfusion-dependent beta-thalassemia (TDT) patients. Methods: The study was conducted at a tertiary health center treating TDT patients. Transient elastography was performed within 3 months of Liver MRI T2* examinations at the radiology department. T-test for independent data or Mann-Whitney U test was used to analyze differences between groups and Spearman correlation with linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and Liver MRI T2* values along with SF levels. Results: In this study on 91 patients, the median age (IQR) of the subjects was 33 (9) years and body mass index was 23.8 (6.1) kg/m2. Median (IQR) TE by fibroscan, MRI T2*(3T), Liver iron concentration (LIC) by MRI Liver T2* and SF levels were 6.38 (2.6) kPa, 32.4 (18) milliseconds, 7(9) g/dry wt., and 1881 (2969) ng/mL, respectively. TE measurements correlated with LIC g/dry wt. (rS =0.39, p=0.0001) and with SF level (rS =0.43, P=0.001) but not with MRI T2* values (rS =-0.24; P=0.98). Conclusion: We observed that in transfusion dependent β thalassemia major patients there was a significant correlation with the TE measured by ultrasound transient elastography, and LIC by MRI as well as SF levels but not with the fibrosis-4 (FIB-4) score. Key Words: Serum ferritin; Fibrosis-4; Transfusion-dependent beta-thalassemia; Transient elastography; Magnetic resonance imaging

Pompe disease is a rare genetic neuromuscular disorder caused by acid α-glucosidase (GAA) deficiency resulting in lysosomal glycogen accumulation and progressive myopathy. Enzyme replacement therapy, the current standard of care, penetrates poorly into the skeletal muscles and the peripheral and central nervous system (CNS), risks recombinant enzyme immunogenicity, and requires high doses and frequent infusions. Lentiviral vector-mediated hematopoietic stem and progenitor cell (HSPC) gene therapy was investigated in a Pompe mouse model using a clinically relevant promoter driving nine engineered GAA coding sequences incorporating distinct peptide tags and codon optimizations. Vectors solely including glycosylation-independent lysosomal targeting tags enhanced secretion and improved reduction of glycogen, myofiber, and CNS vacuolation in key tissues, although GAA enzyme activity and protein was consistently lower compared with native GAA. Genetically modified microglial cells in brains were detected at low levels but provided robust phenotypic correction. Furthermore, an amino acid substitution introduced in the tag reduced insulin receptor-mediated signaling with no evidence of an effect on blood glucose levels in Pompe mice. This study demonstrated the therapeutic potential of lentiviral HSPC gene therapy exploiting optimized GAA tagged coding sequences to reverse Pompe disease pathology in a preclinical mouse model, providing promising vector candidates for further investigation.

The development of tooth is a highly complex procedure and mastered by specific genetic programs. Genetic alterations, environmental factors, and developmental timing can disturb the execution of these programs, and result in various dental anomalies like hypodontia/oligodontia, and supernumerary teeth, which are commonly seen in our clinical practice. Advances in molecular research enabled the identification of various genes involved in the pathogenesis of dental anomalies. In the near future, it will help provide a more accurate diagnosis and biological-based treatment for these anomalies. In this article, we present the molecular phenomenon of tooth development and the genetics of various dental anomalies.

Background. Though vaccines have been reported as highly efficacious in preventing severe COVID-19 disease, there is emerging data of severe infections, albeit a small number, in vaccinated individuals. We have conducted a retrospective observational study to assess the clinical characteristics, immunological response, and disease outcomes among the vaccinated and unvaccinated patients admitted to the ICU with severe COVID-19 disease. Methods. Study Design and Participants. We conducted a retrospective observational study in COVID ICU of a tertiary care hospital. Data were collected from the month of 1 April 2021 to 31 November 2021. All adult patients admitted to the ICU having severe COVID-19 disease were included in the study. Data were collected from the medical records database which included demographics, a clinical course in the ICU, laboratory and radiological parameters, and disease outcomes. In a subset of patients, cell-mediated immunity and S1S2-neutralising antibody assessment was done. Results. A total of 419 patients with severe COVID-19 were included in the study. Of the 419 patients, 90 (21.5%) were vaccinated, and 329 (78.5%) were unvaccinated. There was a significantly higher mortality in unvaccinated severe COVID 19 patients as compared to vaccinated severe COVID patients (46.2% vs 34.4%; P

Chronic stable angina pectoris is the primary indication for ranolazine (RZ), an anti-anginal drug. The drug has an anti-ischemic action that is unaffected by either blood pressure or heart rate. Due to the first-pass effect, the drug has a reduced bioavailability of 35 to 50%. The study emphasized developing a novel transdermal drug delivery system of nanostructured lipid carriers (NLCs) for delivering RZ. Many pharmaceutical companies employ lipid nanoparticles as biocompatible carriers for medicinal, cosmetic, and biochemical uses. These carriers are appropriate for many applications, such as topical, transdermal, parenteral, pulmonary, and oral administration, because of the large variety of lipids and surfactants that are readily available for manufacturing. RZ NLCs were made using high-pressure homogenization. Statistical analysis was utilized to find the best formula by varying the concentrations of Precirol ATO 5 (X1), oleic acid (X2), and Tween 80 (X3). Variables such as entrapment effectiveness (EE) (Y1), particle size (Y2), polydispersity index (PDI) (Y3), and zeta potential (Y4) were tested. A variety of tests were performed on the new formulation to ascertain how well it would be absorbed in the body. These tests included in vivo absorption studies, skin permeability assessments, in vitro drug release assessments, and physicochemical analyses. The particle size of RZ-NLCs was shown to be very small (118.4 ± 5.94 nm), with improved EE (88.39 ± 3.1%) and low ZP and PDI (−41.91 ± 0.38 and 0.118 ± 0.028). SEM and TEM analysis confirmed the structure of the NLCs and showed a smooth, spherical surface. Improved RZ-NLCs were used to create NLC gel, which was then tested for elasticity both physically and rheologically. The formulation’s elasticity was investigated. Optimized RZ-NLCs and NLCG were found to have transdermal fluxes of 48.369 g/cm2/h and 38.383 g/cm2/h, respectively. These results showed that the transdermal delivery of RZ distribution through NLC’s transdermal gel had more significant potential. According to in vivo experiments, the drug’s bioavailability in Wistar rats increased when it was delivered through NLCs. The findings demonstrated that NLCs loaded with RZ successfully transported the RZ to the designated site with no interruptions and that a quadratic connection existed between the independent and dependent variables.

The heterogeneous ecosystems in the Mediterranean Basin (MB) are becoming sensitive to water stress. To investigate the climatic stress, a water budget study was conducted over the basin using TerraClimate simulations for a long temporal range (1990–2020). According to the budget accounting, forested regions received the highest precipitation (P) on average compared to other land use types (annual mean ≈633 mm yr−1), and even then, they were in a water deficit state (−0.42 mm yr−1). Tree plantations in North Africa (Libya and Morocco) were also in a water deficit state; however, their average P was very low (≈12 mm yr−1) compared to that of northern parts of the MB, and the average Actual Evapotranspiration (AET) was ≈15 mm yr−1. Also, the water balance in other land use systems (rain-fed, irrigated croplands, and rangelands) was either negative or near zero. As a whole, the basin’s average annual P was ≈538 mm yr−1, the annual average AET was ≈415 mm yr−1, and the runoff (Q) was equivalent to 123 mm yr−1, which shows a strong influence of ET over the region. Since runoff was negligible in most dry areas, the AET’s large contribution was notable in the North African base of the Atlas Mountains including the Nile delta region. This indicates that precipitation and evaporation are the principal mechanisms of the water balance in the MB. The result shows strong climate variability over Southern Europe, Turkey, and the western Balkans in the recent years, affecting the AET and making their land use systems more vulnerable to water stress. This benchmark study signifies the consistent need for water storage in the Mediterranean vegetation systems of the basin. It also indicates two distinct climate clusters for water balance modeling.

Abstract We hypothesized that the gut microbiome in patients with diabetes secondary to chronic pancreatitis (Type 3c) is different from those with Type 1 and Type 2 diabetes. This was a cross-sectional preliminary study that included 8 patients with Type 1, 10 with Type 2, 17 with Type 3c diabetes and 9 healthy controls. Demographic, clinical, biochemical, imaging and treatment data were recorded and sequencing of the V3–V4 region of the bacterial 16SrRNA was done on fecal samples. Bioinformatics and statistical analyses was performed to evaluate the differences in the diversity indices, distance matrices, relative abundances and uniqueness of organisms between the types of diabetes. There was significant difference in the species richness. Beta diversity was significantly different between patients with Type 3c diabetes and the other groups. 31 genera were common to all the three types of diabetes. There was significant differences in the species level taxa between Type 3c diabetes and the other groups. The unique bacterial species signature in Type 3c diabetes compared to Type 1 and Type 2 diabetes included Nesterenkonia sp. AN1, Clostridium magnum, Acinetobacter lwoffii, Clostridium septicum, Porphyromonas somerae, Terrabacter tumescens, and Synechococus sp.

Background: Medication errors (MEs) are one of the common types of medical errors that have a significant effect on a patient’s health and contribute to mortality and morbidity. This study is designed to detect MEs at King Khalid hospital (KKH) in the Hail region. The objective of this study is to determine the rate, contributing factors, and adverse consequences of MEs at KKH, Hail, Kingdom Saudi Arabia. Method: A retrospective observational study was conducted for 3 months from February to April 2019, the data of a total (586) medication error report forms are collected and analyzed. Main outcome: we have studied the most errors that occur, their main cause, and the person who discovered them. Result: In total 269,179 prescriptions 586 was erroneous, maximum MEs occurred in patients with (16-45) age, improper dose (25.1%) was the frequently observed type of error, majority of MEs were related to antibiotics (21.7%), and anticoagulants (10.1%). The most common cause of MEs is drug information missing, 48.7% of errors are category B according to (NCC MERP) ME index. Pharmacist reports the majority of the MEs and physicians committed most of them. Most MEs occurred in the morning time (71.6%) in the inpatient (66.34%) followed by the outpatient department (26.11%). In MEs 48% of medications administered orally and 41.6% parentally. Conclusion: The rate of MEs in KKH indicate underreporting, the educational programs, sessions, and lectures on the benefits of reporting MEs, a non-punitive culture establishment and remuneration may improve MEs reporting.

Numerous factors can contribute to the development of neurodegenerative disorders (NDs), such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, Huntington’s disease, and multiple sclerosis. Oxidative stress (OS), a fairly common ND symptom, can be caused by more reactive oxygen species being made. In addition, the pathological state of NDs, which includes a high number of protein aggregates, could make chronic inflammation worse by activating microglia. Carotenoids, often known as “CTs”, are pigments that exist naturally and play a vital role in the prevention of several brain illnesses. CTs are organic pigments with major significance in ND prevention. More than 600 CTs have been discovered in nature, and they may be found in a wide variety of creatures. Different forms of CTs are responsible for the red, yellow, and orange pigments seen in many animals and plants. Because of their unique structure, CTs exhibit a wide range of bioactive effects, such as anti-inflammatory and antioxidant effects. The preventive effects of CTs have led researchers to find a strong correlation between CT levels in the body and the avoidance and treatment of several ailments, including NDs. To further understand the connection between OS, neuroinflammation, and NDs, a literature review has been compiled. In addition, we have focused on the anti-inflammatory and antioxidant properties of CTs for the treatment and management of NDs.

Sympatico–vagal balance is essential for regulating cardiac electrophysiology and plays an important role in arrhythmogenic conditions. Various noninvasive methods, including electrocardiography (ECG), have been used for clinical assessment of the sympatico–vagal balance. This study aimed to use a custom-designed wearable device to record ECG and ECG-based cardiac function biomarkers to assess sympatico–vagal balance during tonic pain in healthy controls. Nineteen healthy volunteers were included for the ECG measurements using the custom-designed amplifier based on the Texas Instruments ADS1299. The ECG-based biomarkers of the sympatico–vagal balance, (including heart rate variability, deceleration capacity of the heart rate, and periodic repolarization dynamic), were calculated and compared between resting and pain conditions (tonic pain). The custom-designed device provided technically satisfactory ECG recordings. During exposure to tonic pain, the periodic repolarization dynamics increased significantly (p = 0.02), indicating enhancement of sympathetic nervous activity. This study showed that custom-designed wearable devices can potentially be useful in healthcare as a new telemetry technology. The ECG-based novel biomarkers, including periodic repolarization dynamic and deceleration capacity of heart rate, can be used to identify the cold pressor-induced activation of sympathetic and parasympathetic systems, making it useful for future studies on pain-evoked biomarkers.

A series of 6-aryl substituted pyrimidine azodyes were synthesized by coupling of phenyl pyrimidine 2-amine with different aromatic amines. The synthetic compounds were screened for their in-vitro antioxidant and anti-inflammatory activities. The characterization of the synthesized compounds was carried out by IR, 1H NMR, 13C NMR and Mass spectrophotometry. Computational study of designed compounds was done by OCHEM, Molinspiration cheminformatics, Datawarrior, and Swiss ADME. DPPH assay was used to determine the antioxidant activity and heat hemolysis method for anti-inflammatory activity.

Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.

Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only.

Controlling hyperglycemia and avoiding glucose reabsorption are significant goals in type 2 diabetes treatments. Among the numerous modes of medication administration, the oral route is the most common. Introduction: Dapagliflozin is an oral hypoglycemic agent and a powerful, competitive, reversible, highly selective, and orally active human SGLT2 inhibitor. Dapagliflozin-loaded solid lipid nanoparticles (SLNs) are the focus of our present investigation. Controlled-release lipid nanocarriers were formulated by integrating them into lipid nanocarriers. The nanoparticle size and lipid utilized for formulation help to regulate the release of pharmaceuticals over some time. Dapagliflozin-loaded nanoparticles were formulated by hot homogenization followed by ultra-sonication. The morphology and physicochemical properties of dapagliflozin-SLNs have been characterized using various techniques. The optimized dapagliflozin-SLNs have a particle size ranging from 100.13 ± 7.2 to 399.08 ± 2.4 nm with 68.26 ± 0.2 to 94.46 ± 0.7% entrapment efficiency (%EE). Dapagliflozin-SLNs were optimized using a three-factor, three-level Box–Behnken design (BBD). Polymer concentration (X1), surfactant concentration (X2), and stirring duration (X3) were chosen as independent factors, whereas %EE, cumulative drug release (%CDR), and particle size were selected as dependent variables. Interactions between drug substances and polymers were studied using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and atomic force microscopy (AFM) analysis indicated the crystalline change from the drug to the amorphous crystal. Electron microscope studies revealed that the SLNs’ structure is nearly perfectly round. It is evident from the findings that dapagliflozin-SLNs could lower elevated blood glucose levels to normal in STZ-induced diabetic rats, demonstrating a better hypoglycemic impact on type 2 diabetic patients. The in vivo pharmacokinetic parameters of SLNs exhibited a significant rise in Cmax (1258.37 ± 1.21 mcg/mL), AUC (5247.04 mcg/mL), and oral absorption (2-fold) of the drug compared to the marketed formulation in the Sprague Dawley rats.

Pompe disease is an inherited neuromuscular disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The most severe form is infantile-onset Pompe disease, presenting shortly after birth with symptoms of cardiomyopathy, respiratory failure and skeletal muscle weakness. Late-onset Pompe disease is characterized by a slower disease progression, primarily affecting skeletal muscles. Despite recent advancements in enzyme replacement therapy management several limitations remain using this therapeutic approach, including risks of immunogenicity complications, inability to penetrate CNS tissue, and the need for life-long therapy. The next wave of promising single therapy interventions involves gene therapies, which are entering into a clinical translational stage. Both adeno-associated virus (AAV) vectors and lentiviral vector (LV)-mediated hematopoietic stem and progenitor (HSPC) gene therapy have the potential to provide effective therapy for this multisystemic disorder. Optimization of viral vector designs, providing tissue-specific expression and GAA protein modifications to enhance secretion and uptake has resulted in improved preclinical efficacy and safety data. In this review, we highlight gene therapy developments, in particular, AAV and LV HSPC-mediated gene therapy technologies, to potentially address all components of the neuromuscular associated Pompe disease pathology.

Cobalt nanoparticles (Co-NPs) have been extensively used in clinical practices and medical diagnosis. In this study, the potential toxicity effects of Co-NPs with special emphasis over the biochemical enzyme activities, such as aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in serum, liver, and kidney of Wistar rats were investigated. This toxicity measurement of nanomaterials can support the toxicological data. The biochemical enzymatic variations are powerful tools for the assessment of toxicity. ASAT and ALAT enzymes have been widely used to predict tissue-specific toxicities associated with xenobiotic. The biochemical changes induced by Co-NPs have significance in their toxicological studies because the alterations in biochemical parameters before clinical symptoms indicate either their toxicant safety or detrimental effect. Herein, Co-NPs with particle size

Abstract Carica papaya seeds of a tropical tree comprise water-soluble and positively charged protein known as cystine protease which emerged as a putative coagulant in both water and wastewater treatments. Natural coagulants applications have been posed in many evaluation assays through many years owing to the difficulties raised by usage of chemical coagulants. It is indispensable to optimize process variables such as pH, turbidity, total dissolve solids (TDS), E. coli and coliforms counts accuracy to raise the efficiency of coagulation operation via employing C. papaya. Experimentally, employing jar tests supported by pretreatment, papaya seed protein as a natural coagulant, alum and solar disinfection to remove turbidity and bacteria was accomplished. The results revealed that the removal efficiency for turbidity was culminated up to 100% by incorporation of both alum and C. papaya seeds at lower dosages of coagulant about 0.2–0.6 mg/L at 30 min. A significant difference was found for paired samples correlations around 0.130 by p value = 0, among TDS, C. papaya and alum dosages and turbidity values. Employing a combined process resulted in turbidity and bacteria (most probable numbers of coliforms) removal around 100%. The highest efficiency of solar disinfection system possessed to fell the sunlight exposure period time by up to 2 h with 100% removal of E.coli and coliforms.

According to a recent report by the Iranian industrial organization, over 1700 Industrial and Engineering Brick Manufacturing (IEBM) industries are currently running in Iran, using the same method in common use worldwide. The present research study used a combination of a literature review, existing research reports, and a model of assessment among the four main kinds of IEBM industries to estimate the profit of IEBM using Wastewater Treatment Plant (WWTP) sludge as a model. Paying attention to differences in brick manufacturing practices among the many published papers, we summarized the available standard procedures and methods. Both the paired test and t-test analyses revealed a significant difference among parameters such as initial feed, employees, power, water, fuel, and land (pvalue ≤ 0.001) for the four main types of IEBM industries in Iran. The evaluation identified a priority hierarchy among factors: employees> land > initial feed > water > power > fuel. Therefore, automation in this industry is recommended. Next, two models were developed to estimate the profit of a WWTP and Four Main Brick Manufacturing Industries (FMBMI) using released sludge from the WWTP.

Background: Helicobacter pylori, the cause of most peptic ulcer diseases, infects approximately 50% of the population worldwide. Indian data on cost and effectiveness of the standard first-line therapies for H. pylori eradication are scarce. Thus, the present study was aimed at comparing the cost and efficacy of two standard first-line therapies: Regimen I comprising pantoprazole (40 mg) plus amoxicillin (750 mg) plus clarithromycin (500 mg) (PAC) and Regimen II comprising rabeprazole (20 mg) plus amoxicillin (625 mg) plus metronidazole (200 mg) (RAM). Methodology: This prospective, observational, bottom-up study collected demographic, economic, diagnostic, and therapeutic data from 60 H. pylori-positive patients. The study was carried out for 6 months in the Gastroenterology Department of a Tertiary Care Hospital in Hyderabad, Telangana, India. Results: Health-care system perspective was used to account for direct costs. Average cost per patient for complete H. pylori eradication was Rs. 10,221 and Rs. 8568 for Regimen I and Regimen II, respectively. Inpatient cost was considerably higher than the outpatient cost. Diagnostic costs ranked first in direct costs, followed by hospitalization costs, medication costs, and finally, physician's office visit cost. Individual patient's costs difference between two regimens was found to be statistically significant. Overall, Regimen I proved to be more efficacious than Regimen II, but Regimen II proved to be more cost-effective than Regimen I. Furthermore, incremental cost-effectiveness analysis revealed additional cost of Rs. 127 per patient if the patient was treated with Regimen I instead of Regimen II. Conclusion: Our study showed that Regimen II (RAM) was more cost-effective than Regimen I (PAC), but PAC achieved faster H. pylori eradication than RAM. We assume that this study provides local clinical data as to which regimen may be useful in a particular patient. National Level Clinical Trials are required to further ascertain this conclusion.

Background: Heidelberg retina tomogram (HRT) and optical coherence tomography (OCT) are two widely used imaging modalities to evaluate the optic nerve head (ONH) in glaucoma. Purpose: To compare the ONH parameters of HRT3 and high-definition OCT (HD-OCT) and evaluate their diagnostic abilities in perimetric and preperimetric glaucoma. Design: Cross-sectional analysis. Methods: 35 control eyes (24 subjects), 21 preperimetric glaucoma eyes (15 patients), and 64 perimetric glaucoma eyes (44 patients) from the Longitudinal Glaucoma Evaluation Study underwent HRT3 and HD-OCT examinations. Statistical Analysis: Agreement between the ONH parameters of HRT and HD-OCT were assessed using Bland-Altman plots. Diagnostic abilities of ONH parameters were evaluated using area under the receiver operating characteristic curves (AUCs), sensitivity at fixed specificity, and likelihood ratios (LR). Results: Optic disc area, vertical cup to disc ratio, and cup volume with HD-OCT were larger than with HRT, while the rim area was smaller with HD-OCT (P < 0.001 for all comparisons). AUCs of all HD-OCT ONH parameters (0.90-0.97 in perimetric and 0.62-0.71 in preperimetric glaucoma) were comparable (P > 0.10) to the corresponding HRT ONH parameters (0.81-0.95 in perimetric and 0.55-0.72 in preperimetric glaucoma). LRs associated with diagnostic categorization of ONH parameters of both HD-OCT and HRT were associated with larger effects on posttest probability of perimetric compared to preperimetric glaucoma. Conclusions: ONH measurements of HD-OCT and HRT3 cannot be used interchangeably. Though the diagnostic abilities of ONH parameters of HD-OCT and HRT in glaucoma were comparable, the same were significantly lower in preperimetric compared to perimetric glaucoma.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor belonging to the Per-Arnt-Sim (PAS) family of proteins. The AHR is involved in hematopoietic stem cell (HSC) functions including self-renewal, proliferation, quiescence, and differentiation. We hypothesize that AHR impacts HSC functions by influencing genes that have roles in HSC maintenance and function and that this may occur through regulation of bone marrow (BM) niche cells. We examined BM and niche cells harvested from 8-week-old AHR null-allele (KO) mice in which exon 3 was deleted in the Ahr gene and compared these data to cells from B6 control mice; young and old (10 months) animals were also compared. We report changes in HSCs and peripheral blood cells in mice lacking AHR. Serial transplantation assays revealed a significant increase in long term HSCs. There was a significant increase in mesenchymal stem cells constituting the endosteal BM niche. Gene expression analyses of HSCs revealed an increase in expression of genes involved in proliferation and maintenance of quiescence. Our studies infer that loss of AHR results in increased proliferation and self-renewal of long term HSCs, in part, by influencing the microenvironment in the niche regulating the balance between quiescence and proliferation in HSCs.

Ethacridine lactate (EAL) is an antiseptic in solutions of 0.1%. It is also used as an agent for second trimester abortion. Two simple and sensitive spectrophotometric methods (Method A and Method B) were developed for the estimation of EAL in pharmaceutical formulations. Method A is based on the condensation of the primary aromatic amino group of ethacridine lactate with an aromatic aldehyde (p-Dimethylamino- cinnamaldehyde) to form a chromophore with absorption maximum of 600nm. Method B is based on redox reaction followed by complex formation of EAL with IO3-Metol reagent to form a stable chromogen, which can be estimated at 520 nm. Method A obeys Beer’s law in the concentration range of 2 to 12 μg/mL and method B in the range of 20 to 100 μg/mL. Interference studies were conducted to see the influence of excipients with the proposed methods. The common excipients usually present in dosage forms do not interfere in the proposed method A and method B. The optical characteristics, regression analysis data and precision of the methods were also calculated. The methods were validated for use in routine quality control of EAL in pharmaceutical formulations.

Dysregulation of hematopoietic stem cell (HSC) signaling can contribute to the development of diseases of the blood system. Lack of aryl hydrocarbon receptor (AhR) has been associated with alterations in gene expression related to HSC function and the subsequent development of a myeloproliferative disorder in aging female mice. We sorted the most primitive population of HSCs with the highest stem cell potential (Long-term, or LT-HSCs) from 18-month-old AhR-null-allele (AhR-KO) and WT mice and analyzed gene expression using microarray to determine alterations in gene expression and cell signaling networks in HSCs that could potentially contribute to the aging phenotype of AhR-KO mice. Comparisons with previous array data from 8-week old mice indicated that aging alone is sufficient to alter gene expression. In addition, a significant number of gene expression differences were observed in aged LT-HSCs that are dependent on both aging and lack of AhR. Pathway analysis of these genes revealed networks related to hematopoietic stem cell activity or function. qPCR was used to confirm the differential expression of a subset of these genes, focusing on genes that may represent novel AhR targets due to the presence of a putative AhR binding site in their upstream regulatory region. We verified differential expression of PDGF-D, Smo, Wdfy1, Zbtb37 and Zfp382. Pathway analysis of this subset of genes revealed overlap between cellular functions of the novel AhR targets and AhR itself. Lentiviral-mediated knockdown of AhR in lineage-negative hematopoietic cells was sufficient to induce changes in all five of the candidate AhR targets identified. Taken together, these data suggest a role for AhR in HSC functional regulation, and identify novel HSC AhR target genes that may contribute to the phenotypes observed in AhR-KO mice.

Activation of the FLT3 receptor tyrosine kinase, by point mutations in the second tyrosine kinase domain (TKD), has been described in patients with acute myeloid leukemia (AML). This study was planned to estimate the frequency of FMS-like Tyrosine Kinase 3 Kinase Domain Point Mutation (FLT3/TKD Mutation) D835Y via PCR in different age groups of AML patients. An observational cross sectional study was carried out in National Institute of Blood Diseases and Bone Marrow Transpalntation (NIBD) from May 2010 to October 2011. AML patients diagnosed on the basis of WHO classification of myeloid neoplasms 2008 were included in the study. PCR was used to detect FLT 3/ TKD mutation (D835Y) from peripheral blood samples. DNA was extracted and exon 20 was amplified using primers 20F and 20R. Eco RV restriction enzyme was used to discriminate between mutant D835Y and the wild type followed by 2% agarose gel electrophoresis. A small cohort of cytogenetically unsolicited 151 AML patients were analysed. D835Y mutation was detected in 15 (9.9%) out of 151 patients. D835Y mutation was more frequent approximately double in men (12.1%) than in women (6.7%). The frequency of D835Y mutation increased above 60 years; 2 (14.3%) out of total 14 cases had the mutation in this age group. D835Y mutations were more prevalent in patients with Acute myelomonocytic leukemia (17.6%) followed by AML with maturation (14.9%). In conclusion, FLT3/ TKD mutation has been detected in 9.9% cases of AML patients. It is more commonly seen in male, at increased age and in Acute myelomonocytic leukaemia. Keywords: Acute myeloid leukemia (AML), FLT3, TKD mutation, NIBD, Pakistan