New-onset seizures: an unusual neurologic manifestation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory condition primarily affecting the musculoskeletal system but can often involve other organ systems as well. Rheumatoid meningitis is a rare central nervous system (CNS) manifestation of RA characterized by pachymeningeal and leptomeningeal enhancement. Herein, we present a case of a 64-year-old male who presented with left lower extremity weakness and witnessed seizures. The diagnostic work-up, including lumbar puncture, brain MRI and meningeal biopsy ruled out malignancy and were consistent with the diagnosis of rheumatoid meningitis. The patient was discharged on high-dose steroids along with anti-seizure medications. On subsequent follow-up visits, the patient remained seizure-free.

Outcomes of primary leadless pacemaker implantation: A systematic review.

BACKGROUND: During the last decade, leadless pacemakers (LPMs) have turned into a prevalent alternative to traditional transvenous (TV) pacemakers; however, there is no consolidated data on LPM implantation in emergencies. METHODS: Digital databases were searched for this review and four relevant studies, including 1276 patients were included in this review with procedure duration, fluoroscopic time, major complications, and mortality as primary outcomes and pacing threshold, impedance, sensing of LPM, and hospital stay as secondary outcomes. RESULTS: Gonzales et al. and Marschall et al. showed the duration of the procedure to be 180 ± 45 versus 324.6 ± 92 and 39.9 ± 8.7 versus 54.9 ± 9.8, respectively. Zhang et al. demonstrated the duration of the procedure and fluoroscopy time to be 36 ± 13.4 and 11.1 ± 3.1, respectively. Similarly, Schiavone et al. exhibited intermediate times of implantation at 60 (45-80) versus 50 (40-65) and fluoroscopic times at 6.5 (5-9.7) versus 5.1 (3.1-9). Hospital stay was more with a temp-perm pacemaker as compared to LPM and pacing parameters were not significantly different in all the studies. CONCLUSION: For underlying arrhythmias, whenever appropriate, our review shows that LPMs may be a better option than temporary pacemakers, even as an urgent treatment.

Role of Medicinal Plants in the Management of Inflammatory Disorders: An Overview.

Owing to the enhanced toxicity as well as consequences of allopathic medication, the research on herbal therapies is developing progressively. As a result, medicinal herbs are beginning to play a substantial role in the advancement of the dominant therapeutic medications. Since ancient times, the use of herbs has performed a vital part in human well-being as well in the invention of cutting-edge pharmaceuticals. Inflammation and related illnesses are a major health concern for the entire human population. Pain-inducing drugs including opiates, non-steroidal anti-inflammatory drugs, glucocorticoids, and corticosteroids have severe side effects and these therapies suffer from the recurrence of symptoms too after discontinuing the treatment. As a result, the diagnosis along with the advancement of medications with anti-inflammatory properties is the priority to conquer the drawbacks of the existing therapies. The present review article provides insight into the literature comprising promising phytochemicals from various medicinal plants tested through different model systems and employed for alleviating inflammation in several inflammatory disorders as well as clinical status of the herbal products.

Third-Degree Heart Block in COVID-19 Pneumonia Complicated by Methicillin-Resistant Staphylococcus Aureus (MRSA) Bacteremia. A Case Report and Review of Literature.

Coronavirus disease 2019 (COVID-19) burden has been identified to cause multiorgan damage. Respiratory compromise is still one of the most common presentations, but cardiac injuries like myocardial injury, ischemia, and conduction abnormalities are also becoming prevalent. We present a case of an 87-year-old male with a history of dementia, type 2 diabetes mellitus, hypertension, chronic kidney disease, and a left kidney transplant hospitalized for respiratory distress and generalized tonic-clonic seizures. He was bradycardic to 27 beats per minute, hypotensive with mean arterial pressure <60 mm Hg. An electrocardiogram (EKG) depicted a high-grade atrioventricular block (AV-block). The transvenous pacemaker was placed via femoral access and tested positive for COVID-19. Work-up was done to rule out possible causes of bradycardia, like hypothyroidism, ischemia, AV nodal blocking agents, and drug-induced bradycardia was negative. His hospital stay got complicated by methicillin-resistant staphylococcus aureus (MRSA) pneumonia leading to empyema and bacteremia. Unfortunately, being critically ill, the family opted for comfort measures, and he passed away. Our clinical vignette signifies cardiovascular complications in COVID-19 patients are associated with poor outcomes if not addressed. The conduction abnormalities in patients with intact cardiac structure and function are becoming more common in the setting of COVID infection. Assessment with serial EKGs and cardiac monitoring might be essential as patients can develop AV blocks at any point of the disease.

Bioactive Loaded Novel Nano-Formulations for Targeted Drug Delivery and Their Therapeutic Potential.

Plant-based medicines have received a lot of attention in recent years. Such medicines have been employed to treat medical conditions since ancient times, and in those times only the observed symptoms were used to determine dose accuracy, dose efficacy, and therapy. Rather than novel formulations, the current research work on plant-based medicines has mostly concentrated on medicinal active phytoconstituents. In the past recent decades, however, researchers have made significant progress in developing "new drug delivery systems" (NDDS) to enhance therapeutic efficacy and reduce unwanted effects of bioactive compounds. Nanocapsules, polymer micelles, liposomes, nanogels, phytosomes, nano-emulsions, transferosomes, microspheres, ethosomes, injectable hydrogels, polymeric nanoparticles, dendrimers, and other innovative therapeutic formulations have all been created using bioactive compounds and plant extracts. The novel formulations can improve solubility, therapeutic efficacy, bioavailability, stability, tissue distribution, protection from physical and chemical damage, and prolonged and targeted administration, to name a few. The current study summarizes existing research and the development of new formulations, with a focus on herbal bioactive components.

A cognitive framework based on deep neural network for classification of coronavirus disease.

Since December 2019, the pandemic of coronavirus (CorV) is spreading all over the world. CorV is a viral disease that results in ill effects on humans and is recognized as public health concern globally. The objective of the paper is to diagnose and prevent the spread of CorV. Spatio-temporal based fine-tuned deep learning model is used for detecting Corv disease so that the prevention measures could be taken on time. Deep learning is an emerging technique that has an extensive approach to prediction. The proposed system presents a hybrid model using chest X-ray images to early identify the CorV suspected people so that necessary action can be taken timely. The proposed work consists of various deep learning neural network algorithms for the identification of CorV patients. A decision model with enhanced accuracy has been presented for early identification of the suspected CorV patients and time-sensitive decision-making. A SQueezeNet model is used for the classification of the CorV patient. An experiment has been conducted for validation purposes to register an average accuracy of 97.8%. Moreover, the outcomes of statistical parameters are compared with numerous state-of-the-art decision-making models in the current domain for performance assessment.

Bioactive-Based Cosmeceuticals: An Update on Emerging Trends.

Cosmetic-containing herbals are a cosmetic that has or is claimed to have medicinal properties, with bioactive ingredients purported to have medical benefits. There are no legal requirements to prove that these products live up to their claims. The name is a combination of "cosmetics" and "pharmaceuticals". "Nutricosmetics" are related dietary supplements or food or beverage products with additives that are marketed as having medical benefits that affect appearance. Cosmetic-containing herbals are topical cosmetic-pharmaceutical hybrids intended to enhance the health and beauty of the skin. Cosmetic-containing herbals improve appearance by delivering essential nutrients to the skin. Several herbal products, such as cosmetic-containing herbals, are available. The present review highlights the use of natural products in cosmetic-containing herbals, as natural products have many curative effects as well as healing effects on skin and hair growth with minimal to no side effects. A brief description is given on such plants, their used parts, active ingredients, and the therapeutic properties associated with them. Mainly, the utilization of phytoconstituents as cosmetic-containing herbals in the care of skin and hair, such as dryness of skin, acne, eczema, inflammation of the skin, aging, hair growth, and dandruff, along with natural ingredients, such as for hair colorant, are explained in detail in the present review.

Integration of Dual Stress Transcriptomes and Major QTLs from a Pair of Genotypes Contrasting for Drought and Chronic Nitrogen Starvation Identifies Key Stress Responsive Genes in Rice.

We report here the genome-wide changes resulting from low N (N-W+), low water (N+W-)) and dual stresses (N-W-) in root and shoot tissues of two rice genotypes, namely, IR 64 (IR64) and Nagina 22 (N22), and their association with the QTLs for nitrogen use efficiency. For all the root parameters, except for root length under N-W+, N22 performed better than IR64. Chlorophyll a, b and carotenoid content were higher in IR64 under N+W+ treatment and N-W+ and N+W- stresses; however, under dual stress, N22 had higher chlorophyll b content. While nitrite reductase, glutamate synthase (GS) and citrate synthase assays showed better specific activity in IR64, glutamate dehydrogenase showed better specific activity in N22 under dual stress (N-W-); the other N and C assimilating enzymes showed similar but low specific activities in both the genotypes. A total of 8926 differentially expressed genes (DEGs) were identified compared to optimal (N+W+) condition from across all treatments. While 1174, 698 and 903 DEGs in IR64 roots and 1197, 187 and 781 in N22 roots were identified, nearly double the number of DEGs were found in the shoot tissues; 3357, 1006 and 4005 in IR64 and 4004, 990 and 2143 in N22, under N-W+, N+W- and N-W- treatments, respectively. IR64 and N22 showed differential expression in 15 and 11 N-transporter genes respectively, under one or more stress treatments, out of which four showed differential expression also in N+W- condition. The negative regulators of N- stress, e.g., NIGT1, OsACTPK1 and OsBT were downregulated in IR64 while in N22, OsBT was not downregulated. Overall, N22 performed better under dual stress conditions owing to its better root architecture, chlorophyll and porphyrin synthesis and oxidative stress management. We identified 12 QTLs for seed and straw N content using 253 recombinant inbred lines derived from IR64 and N22 and a 5K SNP array. The QTL hotspot region on chromosome 6 comprised of 61 genes, of which, five were DEGs encoding for UDP-glucuronosyltransferase, serine threonine kinase, anthocyanidin 3-O-glucosyltransferase, and nitrate induced proteins. The DEGs, QTLs and candidate genes reported in this study can serve as a major resource for both rice improvement and functional biology.

Genome sequence and evolution of Betula platyphylla.

Betula L. (birch) is a pioneer hardwood tree species with ecological, economic, and evolutionary importance in the Northern Hemisphere. We sequenced the Betula platyphylla genome and assembled the sequences into 14 chromosomes. The Betula genome lacks evidence of recent whole-genome duplication and has the same paleoploidy level as Vitis vinifera and Prunus mume. Phylogenetic analysis of lignin pathway genes coupled with tissue-specific expression patterns provided clues for understanding the formation of higher ratios of syringyl to guaiacyl lignin observed in Betula species. Our transcriptome analysis of leaf tissues under a time-series cold stress experiment revealed the presence of the MEKK1-MKK2-MPK4 cascade and six additional mitogen-activated protein kinases that can be linked to a gene regulatory network involving many transcription factors and cold tolerance genes. Our genomic and transcriptome analyses provide insight into the structures, features, and evolution of the B. platyphylla genome. The chromosome-level genome and gene resources of B. platyphylla obtained in this study will facilitate the identification of important and essential genes governing important traits of trees and genetic improvement of B. platyphylla.

An Update on the Recent Advances in Cubosome: A Novel Drug Delivery System.

Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form, derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three-dimensional honeycombs like structure provided with two internal aqueous channels for the incorporation of many s biologically active ingredients. In contrast to liposomes, they provide a large surface area for the incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as a method of choice in the sustained release, controlled release, and targeted release dosage forms as new drug delivery system for the better release of the drugs. As a lot of advancement in the new form of dosage form brought the novel avenues in drug delivery mechanisms, so it was a matter of worth to compile the latest updates on the various aspects of the mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health-related benefits.

Severity of violence and quality of life of women with psychiatric disorders as compared to normal controls.

BACKGROUND: Despite the fact that violence against women is a significant public health problem, there is a paucity of research into this area, and little is known about the extent to which women with psychiatric disorders are affected. AIM: The aim of the study was to assess and compare the severity of violence and quality of life of women with psychiatric disorders and normal controls. MATERIALS AND METHODS: Based on purposive sampling technique, a sample consisting of 120 participants was selected from in-patient (female section) and outpatient services of the Ranchi Institute of Neuro-Psychiatry and Allied Sciences and Kanke Area. Both groups were matched on sociodemographic details. Normal controls were screened using General Health Questionnaire-12. The severity of violence against women scale and the revised Conflict Tactics Scale were used to assess the severity of violence, and World Health Organization Quality of Life (WHOQOL)-BREF scale was used for the assessment of the quality of life. Scales were scored as per their test manuals. Results were tabulated and compared using appropriate statistical tests. RESULTS: Women with psychiatric illness as well as normal controls faced various forms of symbolic violence equally. Women with psychiatric disorders faced significantly higher severity of physical assault, sexual coercion, and injury as compared to normal controls. Women with psychiatric disorders had significantly lower scores on WHOQOL BREF compared to normal participants. CONCLUSION: Women with psychiatric disorders suffered significantly higher severity of both physical and sexual violence and had significantly worse quality of life compared to normal controls.

A network of genes associated with poplar root development in response to low nitrogen.

Deployment of the root system is highly sensitive to the levels and spatial distribution of nutrients like nitrogen. However, the genetic determinants of these sensing and deployment mechanisms are still poorly understood. Previously, using system approaches based on temporal changes in root transcriptome in relation to low nitrogen (LN), we have been able to identify a module that activates root production in poplar in response to LN conditions. Here, using comparative, gene ontology and expression analyses, we provide further evidence that the genes in this module are indeed involved in regulation of root development under LN. Better understanding of these modules will enable approaches for breeding for better nitrogen use efficiency through development of a more sensitive and plastic root system.

Bottom-up GGM algorithm for constructing multilayered hierarchical gene regulatory networks that govern biological pathways or processes.

BACKGROUND: Multilayered hierarchical gene regulatory networks (ML-hGRNs) are very important for understanding genetics regulation of biological pathways. However, there are currently no computational algorithms available for directly building ML-hGRNs that regulate biological pathways. RESULTS: A bottom-up graphic Gaussian model (GGM) algorithm was developed for constructing ML-hGRN operating above a biological pathway using small- to medium-sized microarray or RNA-seq data sets. The algorithm first placed genes of a pathway at the bottom layer and began to construct a ML-hGRN by evaluating all combined triple genes: two pathway genes and one regulatory gene. The algorithm retained all triple genes where a regulatory gene significantly interfered two paired pathway genes. The regulatory genes with highest interference frequency were kept as the second layer and the number kept is based on an optimization function. Thereafter, the algorithm was used recursively to build a ML-hGRN in layer-by-layer fashion until the defined number of layers was obtained or terminated automatically. CONCLUSIONS: We validated the algorithm and demonstrated its high efficiency in constructing ML-hGRNs governing biological pathways. The algorithm is instrumental for biologists to learn the hierarchical regulators associated with a given biological pathway from even small-sized microarray or RNA-seq data sets.

A systems biology approach identifies new regulators of poplar root development under low nitrogen.

In Populus, low nitrogen (LN) elicits rapid and vigorous lateral root (LR) proliferation, which is closely mirrored by corresponding transcriptomic changes. Using transcriptomic data, we built a genetic network encompassing a large proportion of the differentially regulated transcriptome. The network is organized in a hierarchical fashion, centered on 11 genes. Transgenic manipulations of only three of the 11 genes had a strong impact on root development under LN. These three genes encoded an F-box protein similar to Hawaiian Skirt (PtaHWS) and two transcription factors (PtaRAP2.11 and PtaNAC1). Up- and downregulation of the three genes caused increased and decreased root proliferation under LN conditions, respectively. The transgenic manipulations had a strong positive effect on growth under greenhouse conditions including increased shoot and root biomass. The three genes appeared to encompass a putative yet-unknown mechanism that underlies root development under LN. Specifically, the genes are predominantly expressed in roots and have a similar temporal response to LN. More importantly, transgenic manipulation for each of the three genes had a highly significant impact on the expression of the other two. The transgenic manipulations appear to also affect the expression of the regulatory miRNA (PtamiRNA164e) of one of the transcription factors (PtaNAC1), albeit in an opposite fashion. Consistent with a putative function of PtaHWS in proteasome degradation, treatment with proteasome inhibitor reversed the expression changes in the transgenic plants. The insights from this study will allow genetic modifications of root architecture for more efficient and dynamic nitrogen foraging in biofuel crops like poplar.

Genetic networks involved in poplar root response to low nitrogen.

Perception of environmental cues and adaptation to changing environmental conditions are crucial for survival of sessile organisms like plants. This is even more important for woody perennial species like trees that can occupy a site for thousands of years. We have previously shown that under low nitrogen (LN), poplar trees display a vigorous and long-lasting root growth associated with global transcriptomic reprogramming and an activation of hierarchical genetic networks. Here we use computational analysis to better understand the network among the genes showing distinct chronological patterns of expression during the response. Our analyses confirm the previous findings, define new potential signaling pathways and the possible downstream targets of these signaling events.

SND1 transcription factor-directed quantitative functional hierarchical genetic regulatory network in wood formation in Populus trichocarpa.

Wood is an essential renewable raw material for industrial products and energy. However, knowledge of the genetic regulation of wood formation is limited. We developed a genome-wide high-throughput system for the discovery and validation of specific transcription factor (TF)-directed hierarchical gene regulatory networks (hGRNs) in wood formation. This system depends on a new robust procedure for isolation and transfection of Populus trichocarpa stem differentiating xylem protoplasts. We overexpressed Secondary Wall-Associated NAC Domain 1s (Ptr-SND1-B1), a TF gene affecting wood formation, in these protoplasts and identified differentially expressed genes by RNA sequencing. Direct Ptr-SND1-B1-DNA interactions were then inferred by integration of time-course RNA sequencing data and top-down Graphical Gaussian Modeling-based algorithms. These Ptr-SND1-B1-DNA interactions were verified to function in differentiating xylem by anti-PtrSND1-B1 antibody-based chromatin immunoprecipitation (97% accuracy) and in stable transgenic P. trichocarpa (90% accuracy). In this way, we established a Ptr-SND1-B1-directed quantitative hGRN involving 76 direct targets, including eight TF and 61 enzyme-coding genes previously unidentified as targets. The network can be extended to the third layer from the second-layer TFs by computation or by overexpression of a second-layer TF to identify a new group of direct targets (third layer). This approach would allow the sequential establishment, one two-layered hGRN at a time, of all layers involved in a more comprehensive hGRN. Our approach may be particularly useful to study hGRNs in complex processes in plant species resistant to stable genetic transformation and where mutants are unavailable.

Evaluation of gene association methods for coexpression network construction and biological knowledge discovery.

BACKGROUND: Constructing coexpression networks and performing network analysis using large-scale gene expression data sets is an effective way to uncover new biological knowledge; however, the methods used for gene association in constructing these coexpression networks have not been thoroughly evaluated. Since different methods lead to structurally different coexpression networks and provide different information, selecting the optimal gene association method is critical. METHODS AND RESULTS: In this study, we compared eight gene association methods - Spearman rank correlation, Weighted Rank Correlation, Kendall, Hoeffding's D measure, Theil-Sen, Rank Theil-Sen, Distance Covariance, and Pearson - and focused on their true knowledge discovery rates in associating pathway genes and construction coordination networks of regulatory genes. We also examined the behaviors of different methods to microarray data with different properties, and whether the biological processes affect the efficiency of different methods. CONCLUSIONS: We found that the Spearman, Hoeffding and Kendall methods are effective in identifying coexpressed pathway genes, whereas the Theil-sen, Rank Theil-Sen, Spearman, and Weighted Rank methods perform well in identifying coordinated transcription factors that control the same biological processes and traits. Surprisingly, the widely used Pearson method is generally less efficient, and so is the Distance Covariance method that can find gene pairs of multiple relationships. Some analyses we did clearly show Pearson and Distance Covariance methods have distinct behaviors as compared to all other six methods. The efficiencies of different methods vary with the data properties to some degree and are largely contingent upon the biological processes, which necessitates the pre-analysis to identify the best performing method for gene association and coexpression network construction.

Cognitive behavioral therapy in the treatment of social phobia.

Cognitive behavior therapy is probably the most well-known and the most practiced form of modern psychotherapy and has been integrated into highly structured package for the treatment of patients suffering from social phobia. The present case study is an attempt to provide therapeutic intervention program to a 27-year-old, unmarried Christian man suffering from social phobia. The patient was treated by using cognitive behavioral techniques. After 17 sessions of therapeutic intervention program, significant improvement was found. He was under follow-up for a period of 6 months and recovered to the premorbid level of functioning.

Possible psychosocial strategies for controlling violence against women.

Women, the fair sex, are considered to be the weaker sex and one of the most powerless and marginalized sections of our society. Violence against women and girls continues to be a global epidemic. It is present in every country, cutting across boundaries of culture, class, education, income, ethnicity and age. A growing body of research studies indicates that 20% to 50% (varying from country to country) of women have experienced domestic violence. A multilayered strategy that addresses the structural causes of violence against women is needed. Strategies and interventions attempting to address violence against women should be guided by 5 underlying principles: Prevention, protection, early intervention, rebuilding the lives of victims/survivors and accountability. When planning interventions, there are a variety of stakeholders who should be borne in mind. Key areas for intervention include encouraging women empowerment; advocacy and awareness raising; education for building a culture of nonviolence; encouraging active participation of women in political system; resource development; direct service provision to victims, survivors and perpetrators; networking and community mobilization; direct intervention to help victims/survivors rebuild their lives; legal reform; monitoring interventions and measures; early identification of 'at risk' families, communities, groups and individuals; and data collection and analysis.