Assessment of clinical,biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 10⁸ WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1β, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid.Level of evidence: IV.     

The relationship between walking and depression,anxiety, and stress among a sample from Jazan,Saudi Arabia: A cross-sectional investigation

This study is aiming to investigate the association between walking and depression, anxiety and stress among adults from Jazan, Saudi Arabia. This study was a cross-sectional investigation where data was collected via an online self-administered questionnaire. The questionnaire had 4 components that measured demographics of the sample, presence of depression, anxiety and stress, and walking history. Differences in median scores of depression, anxiety, and stress according to the measured characteristics were tested via the Mann–Whitney U test. Multivariable logistic regression was performed to estimate odds of reporting depression, anxiety, and stress according to the measured characteristics. A total of 472 adult subjects participated in the current study. The median age of the participants was 23 years, and 52% were males. Half of the participants had variable degrees of depression and anxiety while 39% of the participants had variable degrees of stress. Gender appeared to have the strongest influence on level of depression, anxiety, and stress among the recruited sample (odds ratio 1.8, 2.1, 1.6 respectively (P values < .01). Upon stratifying the sample according to gender, marital status seems to have an association with depression, anxiety, and stress among females (P values < .05). Among males, only walking more than 3 days was associated with the reduction of anxiety (P value .005) and depression (P value .06). This study identified gender difference where walking was not associated with mental health among women but relatively associated among males.     

Prevalence of adverse birth outcomes and associated factors in Jazan,Saudi Arabia: A cross-sectional study

This study aimed to measure the prevalence of adverse birth outcomes and associated factors among mothers from the Jazan region in Saudi, Arabia. This was a cross-sectional investigation where data was collected via a semi-structured questionnaire. The questionnaire was completed during interviews to assess data regarding the participants’ demographics, morbidity, the reported adverse birth outcomes, and maternal complications during pregnancy. Chi-squared and Fisher’s Exact tests were both used to compare the distribution of demographic and obstetric risk factors according to the historical presence of adverse birth outcomes. A total of 1315 women with a combined history of 4950 pregnancies were involved in the current investigation. The mean age of the participants was 33.1 years. The total number of adverse birth outcomes was 1009. The most frequently reported adverse birth outcome was miscarriage (12.1%), followed by premature birth (2.3%) and underweight birth (1.9%). Reports of a minimum of 1 adverse birth outcome were higher among women who reported family incomes of more than 10,000 Saudi Arabian Riyal (SAR), women who were first-degree cousins of their husbands, and women with less than a secondary level education (P values <.05). This study found a relatively high prevalence of miscarriage. Further investigations are needed to assess factors associated with this high frequency level of miscarriage. Furthermore, these findings have preventive and clinical implications concerning pregnant women with a history of obesity, anemia, consanguinity, and hypertension. The goal is to target them with a better range of antenatal care services to reduce the incidence of potential adverse birth outcomes.     

The role of electronic medical records in improving health care quality: A quasi-experimental study

The Teleprimary Care—Oral Health Clinical Information System (TPC-OHCIS) is an updated electronic medical record (EMR) that has been applied in Malaysian primary healthcare. Recognizing the level of patient satisfaction following EMR implementation is crucial for assessing the performance of health care services. Hence, the main objective of this study was to compare the level of patient satisfaction between EMR-based clinics and paper-based clinics.The study was a quasi-experimental design that used a control group and was conducted among patients in 14 public primary healthcare facilities in the Seremban district of Malaysia from May 10, to June 30, 2021. Patient satisfaction was assessed using the validated Short-Form Patient Satisfaction Questionnaire, which consisted of 7 subscales. All data were analyzed using the IBM Statistical Package for Social Sciences version 21.A total of 321 patients consented to participate in this study, and 48.9% of them were from EMR clinics. The mean score for the communication subscale was the highest at 4.08 and 3.96 at EMR-adopted clinics and paper-based record clinics. There were significant differences in general satisfaction and communication subscales, with higher patient satisfaction found in clinics using EMR.With the utilization of EMR, patient satisfaction and communication in delivering healthcare services have improved.     

Weekly Nowcasting of New COVID-19 Cases Using Past Viral Load Measurements

The rapid spread of the coronavirus disease COVID-19 has imposed clinical and financial burdens on hospitals and governments attempting to provide patients with medical care and implement disease-controlling policies. The transmissibility of the disease was shown to be correlated with the patient’s viral load, which can be measured during testing using the cycle threshold (Ct). Previous models have utilized Ct to forecast the trajectory of the spread, which can provide valuable information to better allocate resources and change policies. However, these models combined other variables specific to medical institutions or came in the form of compartmental models that rely on epidemiological assumptions, all of which could impose prediction uncertainties. In this study, we overcome these limitations using data-driven modeling that utilizes Ct and previous number of cases, two institution-independent variables. We collected three groups of patients (n = 6296, n = 3228, and n = 12,096) from different time periods to train, validate, and independently validate the models. We used three machine learning algorithms and three deep learning algorithms that can model the temporal dynamic behavior of the number of cases. The endpoint was 7-week forward number of cases, and the prediction was evaluated using mean square error (MSE). The sequence-to-sequence model showed the best prediction during validation (MSE = 0.025), while polynomial regression (OLS) and support vector machine regression (SVR) had better performance during independent validation (MSE = 0.1596, and MSE = 0.16754, respectively), which exhibited better generalizability of the latter. The OLS and SVR models were used on a dataset from an external institution and showed promise in predicting COVID-19 incidences across institutions. These models may support clinical and logistic decision-making after prospective validation.     

Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell-surface expression

Vascular endothelial growth factor C (VEGF-C) induces lymphangiogenesis via VEGF receptor 3 (VEGFR3), which is encoded by the most frequently mutated gene in human primary lymphedema. Angiopoietins (Angs) and their Tie receptors regulate lymphatic vessel development, and mutations of the ANGPT2 gene were recently found in human primary lymphedema. However, the mechanistic basis of Ang2 activity in lymphangiogenesis is not fully understood. Here, we used gene deletion, blocking Abs, transgene induction, and gene transfer to study how Ang2, its Tie2 receptor, and Tie1 regulate lymphatic vessels. We discovered that VEGF-C–induced Ang2 secretion from lymphatic endothelial cells (LECs) was involved in full Akt activation downstream of phosphoinositide 3 kinase (PI3K). Neonatal deletion of genes encoding the Tie receptors or Ang2 in LECs, or administration of an Ang2-blocking Ab decreased VEGFR3 presentation on LECs and inhibited lymphangiogenesis. A similar effect was observed in LECs upon deletion of the PI3K catalytic p110α subunit or with small-molecule inhibition of a constitutively active PI3K located downstream of Ang2. Deletion of Tie receptors or blockade of Ang2 decreased VEGF-C–induced lymphangiogenesis also in adult mice. Our results reveal an important crosstalk between the VEGF-C and Ang signaling pathways and suggest new avenues for therapeutic manipulation of lymphangiogenesis by targeting Ang2/Tie/PI3K signaling.     

Peri- and postnatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: effects on physiological development,reflexes, locomotor activity and learning behaviour in Wistar rats

 Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the development of rat offspring were studied after administration of a loading dose of 300 or 1000 ng TCDD/kg body wt on day 19 of pregnancy, followed by weekly maintenance doses of 120 or 400 ng TCDD/kg body wt. The dose regimens led to a fluctuation of average TCDD concentrations in the liver of the offspring of 4.9–14.9 ng/g (TCDD1000/400 group) or 1.4–6.3 ng/g (TCDD300/120 group) during the course of the experiment. In both TCDD-exposed groups the body weight of the offspring was significantly lower on postnatal day 7 (PND 7); in the high dose group from PND 7 to PND 31. Some landmarks of postnatal development were retarded in the exposed groups; in particular, the vaginal opening was delayed for several days in both TCDD-exposed groups. The TCDD-exposed animals revealed a reduced ability to remain on a rotating rod. During reflex testing, the rate of successfully responding animals was higher in the exposed groups. No statistically significant differences in the locomotor activity between controls and TCDD-exposed offspring were detectable under our experimental conditions. In a discrimination learning test no effects on the learning ability were found. However, TCDD-exposed offspring showed an increase in unanswered trials during critical phases of the task. They also exhibited increased locomotor activity in a novel environment; prior to an amphetamine challenge dose of 1 mg/kg body weight. Amphetamine-induced activity was decreased in a dose-dependent manner. Received: 2 May 1994 / Accepted: 13 July 1994     

Investigation of antioxidant compounds in commercial pomegranate molasses products using matrix-solid phase dispersion extraction coupled with HPLC

Pomegranate is a well known fruit for its unique flavor, taste and health benefits. The medicinal properties of this fruits directly associated with the phenolic content present, with great anti-oxidant potential. The research is intended to develop matrix solid phase dispersion method (MSPD) and HPLC quantification of four major anti-oxidant marker constituents (vitamin C, gallic acid, rutin & ellagic acid) in pomegranate molasses samples. The effects of several important experimental parameters like type of dispersant, sample-dispersant ratio, solvents and its volume, time of extraction were investigated. A C₁₈ column with the specification (5?µm, 250?×?4.0?mm) was used for the separation. A gradient flow of mobile phase was selected after many trials containing 0.1%, v/v solution of orthophosphoric acid and acetonitrile. The flow rate was 1.0?mL/min; and the chromatograms were recorded at 254?nm. The validation parameters, like linearity (r²?=?0.9985, 0.9965, 0.9925 & 0.9986), accuracy (100.3, 99.5, 100.9 & 101.9%), intra-day precision (%RSD?=?1.09, 1.02, 1.26 & 0.97), inter-day precision (%RSD?=?1.32, 0.83, 1.07, & 1.15) LOD (0.07, 4.50, 0.45 & 0.40?µg/mL), LOQ (0.095, 9.50, 0.85 & 9.5?µg/mL) and robustness (% RSD?=?0.92, 0.76, 0.81 & 0.83) respectively for vitamin C, gallic acid, rutin & ellagic acid, were found satisfactory as per ICH guidelines.     

Optimization and evaluation of lyophilized fenofibrate nanoparticles with enhanced oral bioavailability and efficacy

Abstract

The objective of this study was to enhance physiochemical properties as well as oral bioavailability of the poorly water soluble drug fenofibrate (FB), through preparation of amorphous solid dispersions (ASDs). ASDs were prepared via freeze drying using polyvinylpyrrolidone (PVP) K30 and poloxamer 188 as hydrophilic carriers. Formulations were optimized by 3² full factorial design (FFD) with PVP-K30 level (X₁) and poloxamer 188 level (X₂) as independent variables and particle size (Y₁), zeta potential (Y₂), drug content (Y₃) and dissolution rate (T90, [Y₄]) as dependent variables. Optimized FB nanoparticles were physicochemically evaluated and formulated into lyophilized sublingual tablets. Pharmacokinetic, pharmacodynamics and histological finding of optimized formulation were performed on rabbits. Y₁ and Y₄ were significantly affected by independent variables while Y₂ and Y₃ were not affected. Physicochemical characterization showed the drug was in amorphous state, nanometer range and pharmacophore of FB was preserved. Administration of optimized FB tablets to rabbits with fatty liver led to significant reduction (p?<?0.001) in serum lipids. Moreover, histological analysis of liver specimens confirmed the improved efficacy in animals with fatty liver. In this study, we confirmed that ASDs of FB had beneficial effects on managing fatty liver and serum lipids level in hyperlipidemic rabbits.