Impact of Hyperuricemia and Urate-Lowering Agents on Cardiovascular Diseases.

The association between hyperuricemia and cardiovascular diseases has been studied for many years. Research has shown a link between high uric acid levels and increased risk of including coronary artery disease hypertension and other cardiovascular conditions. Urate-lowering therapy, particularly with xanthine oxidase inhibitors like allopurinol, has shown promising results in reducing blood pressure in individuals with hyperuricemia and hypertension. Clinical trials and studies have demonstrated significant reductions in both systolic and diastolic blood pressure with urate-lowering treatment. Urate-lowering treatment has shown a favorable effect on reducing systolic blood pressure and major adverse cardiovascular events in patients with previous cardiovascular disease. In terms of cardiovascular safety, clinical trials have indicated that xanthine oxidase inhibitors such as febuxostat are non-inferior to allopurinol and do not increase the risk of death or serious adverse events. Overall, these findings highlight the importance of managing hyperuricemia and utilizing urate-lowering therapy to mitigate the adverse cardiovascular effects associated with elevated uric acid levels.

Role of genetic polymorphisms in clopidogrel response variability: a systematic review.

INTRODUCTION: Clopidogrel is a P2Y12 inhibitor that has become a mainstay treatment following percutaneous intervention with drug-eluting stent placement to decrease restenosis and its potential complications, including sudden cardiac death and ischaemic strokes in patients with significant vascular disease. AREAS COVERED: As a prodrug, the metabolism and efficacy of clopidogrel are contingent on the presence of wild-type CYP450 (CYP2C19) alleles. Genetic polymorphisms and variants are well known to impair its ability to prevent major adverse cardiovascular events in these patients, with inadequate response rates as high as 30% in previous publications. Patterns of allelic frequencies are expected to exhibit similarities between individuals of the same ancestry, ethnic group or geographic region. Accordingly, we seek to further elucidate worldwide prevalence rates for genetic polymorphisms in the CYP2C19-dependent metabolism of clopidogrel and review the potential of personalised CYP2C19 genotyping in clinical practice to mitigate this high treatment resistance and its associated burden on patients. EXPERTS' COMMENTARY: Our findings support the consideration of genotyping before initiation of therapy to guide adequate dosage or substitutions of other P2Y12 inhibitors to promote personalised, precision medicine and to prevent adverse events when these therapies may inevitably fail in patients with variants of the CYP450 (CYP2C19) system.

COVID-19-Induced Cardiac Tamponade: A Case Study and a Literature Review.

COVID-19 presentation is heterogeneous. As a viral illness, it could cause pericardial effusion leading to cardiac tamponade. We present a patient coursing with this viral illness that was found to have cardiac tamponade. We report a case of a 79-year-old female who presented with shortness of breath and dry cough for one week and resulted positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Her initial chest X-ray showed a bottle-shaped heart. Computed chest tomography showed pericardial effusion, and an echocardiogram confirmed moderated pericardial effusion with signs of tamponade. He improved with conservative therapy with colchicine, ibuprofen, cefepime, dexamethasone, dolutegravir, and apixaban for pulmonary emboli. An early approach in cardiac tamponade induced by COVID-19 is crucial to promptly address an aggressive directed therapy, avoiding potential complications or unnecessary procedures.

Impact of Cross-Validation on Machine Learning Models for Early Detection of Intrauterine Fetal Demise.

Intrauterine fetal demise in women during pregnancy is a major contributing factor in prenatal mortality and is a major global issue in developing and underdeveloped countries. When an unborn fetus passes away in the womb during the 20th week of pregnancy or later, early detection of the fetus can help reduce the chances of intrauterine fetal demise. Machine learning models such as Decision Trees, Random Forest, SVM Classifier, KNN, Gaussian Naïve Bayes, Adaboost, Gradient Boosting, Voting Classifier, and Neural Networks are trained to determine whether the fetal health is Normal, Suspect, or Pathological. This work uses 22 features related to fetal heart rate obtained from the Cardiotocogram (CTG) clinical procedure for 2126 patients. Our paper focuses on applying various cross-validation techniques, namely, K-Fold, Hold-Out, Leave-One-Out, Leave-P-Out, Monte Carlo, Stratified K-fold, and Repeated K-fold, on the above ML algorithms to enhance them and determine the best performing algorithm. We conducted exploratory data analysis to obtain detailed inferences on the features. Gradient Boosting and Voting Classifier achieved 99% accuracy after applying cross-validation techniques. The dataset used has the dimension of 2126 × 22, and the label is multiclass classified as Normal, Suspect, and Pathological condition. Apart from incorporating cross-validation strategies on several machine learning algorithms, the research paper focuses on Blackbox evaluation, which is an Interpretable Machine Learning Technique used to understand the underlying working mechanism of each model and the means by which it picks features to train and predict values.

Diuretic resistance and the role of albumin in congestive heart failure.

Diuresis with loop diuretics is the mainstay treatment for volume optimization in patients with congestive heart failure, in which perfusion and volume expansion play a crucial role. There are robust guidelines with extensive evidence for the management of heart failure; however, clear guidance is needed for patients who do not respond to standard diuretic treatment. Diuretic resistance (DR) can be defined as an insufficient quantity of natriuresis with proper diuretic therapy. A combination of diuretic regimens is used to overcome DR and, more recently, SGLT2 inhibitors have been shown to improve diuresis. Despite DR being relatively common, it is challenging to treat and there remains a notable lack of substantial data guiding its management. Moreover, DR has been linked with poor prognosis. This review aims to expose the multiple approaches for treatment of patients with DR and the importance of intravascular volume expansion in the response to therapy.

Interactions between Fermi polarons in monolayer WS2.

Interactions between quasiparticles are of fundamental importance and ultimately determine the macroscopic properties of quantum matter. A famous example is the phenomenon of superconductivity, which arises from attractive electron-electron interactions that are mediated by phonons or even other more exotic fluctuations in the material. Here we introduce mobile exciton impurities into a two-dimensional electron gas and investigate the interactions between the resulting Fermi polaron quasiparticles. We employ multi-dimensional coherent spectroscopy on monolayer WS2, which provides an ideal platform for determining the nature of polaron-polaron interactions due to the underlying trion fine structure and the valley specific optical selection rules. At low electron doping densities, we find that the dominant interactions are between polaron states that are dressed by the same Fermi sea. In the absence of bound polaron pairs (bipolarons), we show using a minimal microscopic model that these interactions originate from a phase-space filling effect, where excitons compete for the same electrons. We furthermore reveal the existence of a bipolaron bound state with remarkably large binding energy, involving excitons in different valleys cooperatively bound to the same electron. Our work lays the foundation for probing and understanding strong electron correlation effects in two-dimensional layered structures such as moiré superlattices.

Environmentally benign approach for the efficient sequestration of methylene blue and coomassie brilliant blue using graphene oxide emended gelatin/κ-carrageenan hydrogels.

Herein, we report the synthesis and characterization of gelatin/κ-carrageenan crosslinked polyacrylic acid hydrogel (GT-CAG-cl-polyAA) and graphene oxide incorporated hydrogel nanocomposite (GOHNC) through a free radical crosslinking pathway. Under optimized reaction conditions, GT-CAG-cl-polyAA displayed 486 % maximum swelling percentage. TEM image depicted wrinkled silk veil wave-type surface morphology of graphene oxide (GO), whereas, the SEM analysis indicated the porous nature of the GT-CAG-cl-polyAA and GOHNC capable of accumulating a large number of water/dye molecules. GT-CAG-cl-polyAA exhibited 96.11 % and 82.16 % dye removal potential for the adsorption of methylene blue (MB) and coomassie brilliant blue (CB), respectively under optimized conditions. GOHNC enhanced the % dye removal efficiency (98.39 % for MB and 94.50 % for CB). The maximum adsorption capacity of GOHNC for the removal of CB and MB was 312.7 mg/g and 94.9 mg/g, respectively. The adsorption of CB and MB exhibited best fitting with Flory-Huggins adsorption isotherms data. The negative values of ΔG° and positive values of ΔS° which were obtained from the adsorption isotherm plot suggested the thermodynamic feasibility of the adsorption. Also, the samples were reusable for up to five consecutive cycles without any degradation and hence suggested a considerable pathway for the separation of textile dyes.

Toward nanotechnology-enabled face masks against SARS-CoV-2 and pandemic respiratory diseases.

Wearing a face mask has become a necessity following the outbreak of the coronavirus (COVID-19) disease, where its effectiveness in containing the pandemic has been confirmed. Nevertheless, the pandemic has revealed major deficiencies in the ability to manufacture and ramp up worldwide production of efficient surgical-grade face masks. As a result, many researchers have focused their efforts on the development of low cost, smart and effective face covers. In this article, following a short introduction concerning face mask requirements, the different nanotechnology-enabled techniques for achieving better protection against the SARS-CoV-2 virus are reviewed, including the development of nanoporous and nanofibrous membranes in addition to triboelectric nanogenerators based masks, which can filter the virus using various mechanisms such as straining, electrostatic attraction and electrocution. The development of nanomaterials-based mask coatings to achieve virus repellent and sterilizing capabilities, including antiviral, hydrophobic and photothermal features are also discussed. Finally, the usability of nanotechnology-enabled face masks is discussed and compared with that of current commercial-grade N95 masks. To conclude, we highlight the challenges associated with the quick transfer of nanomaterials-enabled face masks and provide an overall outlook of the importance of nanotechnology in counteracting the COVID-19 and future pandemics.

Effect of vitamins and metal ions on productivity and charge heterogeneity of IgG1 expressed in CHO cells.

Recombinant monoclonal antibodies have emerged as the most successful modality of biotherapeutics. They are primarily expressed in Chinese Hamster Ovary (CHO) cells. It is well known that post-translational modifications (PTM) contribute significantly to heterogeneity with respect to charge, glycosylation, and size. These attributes in turn impact stability, pharmacokinetics, and pharmacodynamics of the biotherapeutic product. Cell culture media components are known to significantly contribute to both cellular productivity as well as post-translational modifications. Thus, it is highly desirable to understand how media components affect product quality. This study aims to explore the impact of vitamins and metal ions on protein expression and post-translational modifications specifically charge heterogeneity. Biotin, choline chloride, D-calcium pantothenate, folic acid, pyridoxine hydrochloride, thiamine hydrochloride vitamins and Fe, Cu, Mg, Co, Zn, Mn, Ni metal ions were examined in this study. The results indicate that pyridoxine enhances productivity while Zn, Cu, Fe, Mn, and biotin impact charge heterogeneity. While, Fe, Mn and Ni enhance production of the acidic variants, Cu and biotin inhibit it. Zn reduces formation of basic variants while biotin enhances it. The results from this investigation could be used for process control so as to get consistent charge variant profile, in particular for biosimilars.

Prevalence of musculoskeletal complaints and juvenile idiopathic arthritis in children from a developing country: a school-based study.

INTRODUCTION: Musculoskeletal complaints are common in children. Studies from developed countries have found most to be non-inflammatory and juvenile idiopathic arthritis (JIA) to be less than 0.1%. However, there is limited data from developing countries such as India. METHODS: This cross-sectional study was conducted from March 2010 to April 2011 among school children aged 6-17 years in northern India. Prevalence of musculoskeletal complaints and JIA were determined using a questionnaire on musculoskeletal complaints. This was filled either by parents (always in children < 14 years) or children themselves. Subsequently, all children were individually met and responses verified. An abbreviated musculoskeletal examination (GALS) was performed on every child. In cases of suspected inflammatory arthritis, further investigations were performed. RESULTS: Of the 2059 children (851 girls, 1208 boys) who were included in this study, mean (± SD) age was 11.5 ± 2.9 years. Joint pain (more than 1 week) was present in 158 (7.6%), back pain in 63 (3.1%) and heel pain in 62 (3%) of them. Limb pains, suggestive of 'growing pains', were present in 45 (2.1%) children. There were six suspected cases of inflammatory musculoskeletal pain; however, only one child was confirmed as having JIA (enthesitis-related arthritis). The estimated prevalence of JIA was 48/100,000 in Indian children. CONCLUSION: Musculoskeletal complaints were not uncommon in children from a developing country like India. Estimated prevalence of JIA was 48/100,000 (95%CI 10-280).

Does 'weight reduction' help all adult snorers?

BACKGROUND: Obesity is now a global epidemic. Obese people are at higher risk of snoring. Weight reduction could influence the prevalence of snoring. Present study tried to find out, whether weight reduction is of benefit in all adult snorers. MATERIALS AND METHODS: It is a cross sectional study, on 349 subjects (196 males and 153 females). They and their spouses were asked for snoring habits. Their neck circumference, height and weight was measured and Body mass index (BMI) was calculated, and they were classified into low normal, high normal, pre-obese and obese BMI groups. Prevalence rates of snoring in different groups were compared, to find out any statistically significant difference, between them. RESULTS: Statistically significant difference, in prevalence rates of snoring was found, when obese and pre-obese group were compared with normal BMI group, separately. No significant difference was found in prevalence rates, when comparison was made between obese and pre-obese group. Difference in prevalence of snoring, was also not significant, when comparison was made between low normal and high normal BMI groups. Neck circumference of snorers was significantly more than the neck circumference of non-snorers in all BMI groups. Gender wise difference, in prevalence of snoring was also not significant. CONCLUSION: Body mass index target needs to be set at 25 kg/m(2), in weight reduction programmes, to achieve clinically relevant response in a snorer. There is no need to put extra emphasis, on further reduction of BMI. Weight reduction, is not helpful in all adult snorers, especially those with normal BMI, where other causes of snoring, like fat around upper airways, need to be considered.

Development and evaluation of ethyl cellulose-based transdermal films of furosemide for improved in vitro skin permeation.

Transdermal films of the furosemide were developed employing ethyl cellulose and hydroxypropyl methylcellulose as film formers. The effect of binary mixture of polymers and penetration enhancers on physicochemical parameters including thickness, moisture content, moisture uptake, drug content, drug-polymer interaction, and in vitro permeation was evaluated. In vitro permeation study was conducted using human cadaver skin as penetration barrier in modified Keshary-Chein diffusion cell. In vitro skin permeation study showed that binary mixture, ethyl cellulose (EC)/hydroxypropyl methylcellulose (HPMC), at 8.5:1.5 ratio provided highest flux and also penetration enhancers further enhanced the permeation of drug, while propylene glycol showing higher enhancing effect compared to dimethyl sulfoxide and isopropyl myristate. Different kinetic models, used to interpret the release kinetics and mechanism, indicated that release from all formulations followed apparent zero-order kinetics and non-Fickian diffusion transport except formulation without HPMC which followed Fickian diffusion transport. Stability studies conducted as per International Conference on Harmonization guidelines did not show any degradation of drug. Based on the above observations, it can be reasonably concluded that blend of EC-HPMC polymers and propylene glycol are better suited for the development of transdermal delivery system of furosemide.