Severe acute respiratory syndrome Coronavirus-2 GenoAnalyzer and mutagenic anomaly detector using FCMFI and NSCE.

In order to deepen our understanding of the virus and help guide the creation of efficient therapies, this study uses artificial intelligence tools to thoroughly explore the genetic sequences of the SARS-CoV-2 virus. The process starts by using the Fuzzy Closure Miner for Frequent Itemsets (FCMFI) on a large corpus of SARS-CoV-2 genomic sequences to reveal hidden patterns, including nucleotides base sequences, repeating motifs, and corresponding interchanges. Then, using the Nucleotide Sequence Comprehension Engine (NSCE) technique, we were able to precisely define the genomic areas for mutation analysis. Structured and unstructured proteins are both strongly impacted by virus mutations, with spike proteins that are linked to the severity of COVID-19 pneumonia being particularly affected. Notably, the Mutagenic Anomaly Detector shows a 65 % efficiency boost in computing genome mutation rates compared to conventional point mutation analysis, while GenoAnalyzer offers a remarkable 93.33 % improvement over existing approaches in recognizing common genomic sequence patterns. These results highlight the potential of FCMFI to reveal complex genomic patterns and significant insights in COVID-19 genetic sequences when combined with mutation analysis. The Mutagenic Anomaly Detector and GenoAnalyzer show promise for revealing hidden genomic patterns and precisely estimating the SARS-CoV-2 mutation rate.

A Novel NOX Inhibitor Alleviates Parkinson's Disease Pathology in PFF-Injected Mice.

Oxidative stress-mediated damage is often a downstream result of Parkinson's disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2 and 4. Utilizing N27 rat dopaminergic cells and C57Bl/6 mice, we confirmed that the exposures of alpha-synuclein preformed fibrils (PFF) induced protein aggregation, a hallmark in PD pathology. In vitro assessment of the novel compound revealed an increase in cell viability and decreases in cytotoxicity, ROS, and protein aggregation (Thioflavin-T stain) against PFF exposure at the optimal concentration of 10 nM. Concomitantly, the oral treatment alleviated motor-deficits in behavioral tests, such as hindlimb clasping, rotarod, pole, nesting and grooming test, via reducing protein aggregation, based on rescued dopaminergic neuronal loss. The suppression of NOX-1, 2 and 4 within the striatum and ventral midbrain regions including Substantia Nigra compacta (SNc) contributed to neuroprotective/recovery effects, making it a potential therapeutic option for PD.

Is optic nerve sheath diameter a promising screening tool to predict neurological outcomes and the need for secondary decompressive craniectomy in moderate to severe head injury patients? A prospective monocentric observational pilot study.

Background: Optic nerve sheath diameter (ONSD) has been shown to be a noninvasive and quick method to calculate intracranial pressure (ICP) and subsequent neurologic outcomes, although with variable cutoffs. ICP can be indirectly assessed by noninvasive methods such as transcranial Doppler, ONSD, tympanic membrane displacement, and fundoscopy. Knowledge regarding the diagnostic accuracy of ONSD for predicting unfavorable outcomes within 72 hours (h) of moderate and severe head injury is limited. The objective of this study was to measure ONSD measurements at 24-h intervals in moderate to severe head injury patients and to find its association with clinical outcomes in the target population. Methods: This prospective observational study was done on moderate to severe head injury patients. ONSD was measured twice at 24-h intervals over 48 h. The clinical outcome was divided into the favorable group (patients who were in conservative treatment with a stable Glasgow Coma Scale [GCS] score and discharged following treatment) and the unfavorable group (patients who had a drop in GCS motor score of one or more, or expired or underwent surgical intervention) within 72 h following traumatic brain injury. The Kruskal-Wallis test, Mann- Whitney test, and receiver operating characteristic curves were used to establish the association between ONSD and clinical outcomes. Results: ONSD values measured at 24-h intervals >6.1 mm (P < 0.0146) and 6.2 mm (P < 0.0001) were found to be predictors of unfavorable outcomes (expired or underwent surgery), and hence the need for a secondary decompressive craniectomy (DC). Conclusion: ONSD is an efficient screening tool to assess neurological outcomes in severe head injury patients. It can reliably predict the need for secondary DC at an earlier stage before secondary brain damage ensues in these patients.

Can Amoxicillin and Clavulanic Acid Impregnated Plaster of Paris Beads Serve as an Effective Alternative to Systemic Antibiotics for Third Molar Surgeries? A Split Mouth Randomized Clinical Trial.

Purpose: The present work was a pilot study undertaken to evaluate the effectiveness of amoxicillin and clavulanic acid impregnated plaster of paris beads for prevention of infection of third molar extraction sockets. Materials and Methods: This was a prospective, randomized, split mouth clinical trial done on 16 patients (32 sites) who required surgical extraction of mandibular third molars. Control arm patients were given Tab. amoxicillin 500 mg with clavulanic acid 125 mg (Tab. Klavimed 625 mg, Indomed, India), thrice daily for 3 days after extraction, whereas test arm patients received Antibiotic Impregnated Microbeads (AIM), containing Amoxicillin 500 mg and Clavulanic Acid 100 mg placed in situ in the extraction socket. The primary outcome parameter was infection and the secondary outcome parameters were pain, trismus, swelling and wound healing. Results: None of the patients in either group had post operative infection. There was no significant difference in pain intensity between the two groups (1st day p = 0.41; 3rd day p = 0.38, 7th day p = 0.37). Both the groups were also similar with respect to swelling (p = 0.596, 0.146, 0.871, 0.820 on 1st, 3rd, 7th, 15th post-op day ,respectively). Conclusion: Amoxycillin with clavulanic acid impregnated PoP beads appears to be as effective as oral 3 day amoxicillin with clavulanic acid regime for prevention of 3 M socket infection.

Reinforcement of nanoporous lanthanum-doped zinc borate by vanadium selenide nanosheets for improved tribological activity.

Nanoporous zinc borate (ZB) and 10% lanthanum-doped porous zinc borate (LZB) were synthesized to explore the role of porosity and doping in zinc borate during lubrication. HR-SEM, TEM, and HR-TEM authenticated nanoporous structures. The tribological properties of their blends with paraffin oil (PO) were compared by employing ASTM D4172 and ASTM D5183 norms on a four-ball tester. Vanadium selenide nanosheets (VSe2) were used to reinforce the structure of LZB for further advancement of the tribological properties. The superiority of the LZB/VSe2 over LZB and VSe2 nanosheets could be adjudged by tribological data. The porosity and lanthanum doping have yielded commendable tribological activity. The VSe2 nanosheets have strengthened the LZB matrix. The other constituent oxides of tribofilm from the LZB matrix, based on EDX analysis and XPS studies of the worn surface, ZnO, B2O3, La2O3, and V2O5, have abetted lubrication. The AFM and SEM investigations of wear track corroborated the tribological results.

Applications of artificial intelligence and machine learning in orthognathic surgery: A scoping review.

Over the recent years, Artificial Intelligence (AI) has been progressing rapidly with its ability to mimic human cognitive functions. The potential applications of AI technology in diagnosis, treatment planning, and prognosis prediction have been demonstrated in various studies. The present scoping review aimed to provide an overview of AI and Machine Learning (ML) algorithms and their applications in orthognathic surgery. A comprehensive search was conducted in databases including PubMed, Embase, Scopus, Web of Science and OVID Medline until November 2021. This scoping review was conducted following the PRISMA-ScR guidelines. After applying the inclusion and exclusion criteria, a total of 19 studies were included for final review. AI has profoundly impacted the diagnosis and prediction of orthognathic surgeries with a clinically acceptable accuracy range. Furthermore, AI reduces the work burden of the clinician by eliminating the tedious registration procedures, thereby helping in efficient and automated planning. However, focussing on the research gaps, there is a need to foster the AI models/algorithms to contemporize their efficiency in clinical decision making, diagnosis and surgical planning in future studies.

A Novel NOX Inhibitor Treatment Attenuates Parkinson's Disease-Related Pathology in Mouse Models.

Parkinson's disease (PD) is a progressive neurodegenerative motor disorder without an available therapeutic to halt the formation of Lewy bodies for preventing dopaminergic neuronal loss in the nigrostriatal pathway. Since oxidative-stress-mediated damage has been commonly reported as one of the main pathological mechanisms in PD, we assessed the efficacy of a novel NOX inhibitor from AptaBio Therapeutics (C-6) in dopaminergic cells and PD mouse models. The compound reduced the cytotoxicity and enhanced the cell viability at various concentrations against MPP+ and α-synuclein preformed fibrils (PFFs). Further, the levels of ROS and protein aggregation were significantly reduced at the optimal concentration (1 µM). Using two different mouse models, we gavaged C-6 at two different doses to the PD sign-displaying transgenic mice for 2 weeks and stereotaxically PFF-injected mice for 5 weeks. Our results demonstrated that both C-6-treated mouse models showed alleviated motor deficits in pole test, hindlimb clasping, crossbeam, rotarod, grooming, and nesting analyses. We also confirmed that the compound treatment reduced the levels of protein aggregation, along with phosphorylated-α-synuclein, in the striatum and ventral midbrain and further dopaminergic neuronal loss. Taken together, our results strongly suggest that NOX inhibition can be a potential therapeutic target for PD.

A retrospective study on factors affecting the dropout rate among temporomandibular joint internal disc derangement patients in India - A single-institution experience.

Introduction: Patients suffering temporomandibular joint internal disc derangement (IDD) ignore appointments after the first examination or after the first or second sessions of initial treatment. The dropout rate for these patients varies from 36% to 78% as per literature. Unfortunately, very few studies have investigated the dropout rate of these patients. Hence, the present study was undertaken to find out the dropout rate among these kinds of patients. Material and Methods: A retrospective study was done from June 2008 to December 2017 by collecting the records of the patients who were diagnosed to have IDD. Outcome variables included were age, sex, distance traveled, occupation, and education. Results: Out of 1021 patients 766 patients were included in the study after fulfilling the inclusion and exclusion criteria. The data were analyzed using Chi-square test. The level of significance was set at <0.05. In this study, there is slight male predominance (52.8%) and 63.1% (21-40 years) were among young adults and the patients in the age group of 21-30 years had shown good compliance, Postgraduate has shown the highest follow-up rate when compared with graduates and school level and the difference was found to be statistically significant. People in the job had shown good compliance when compared with business class and retired people and the patients within 50 km had shown the maximum follow-up with a statistically significant difference (P < 0.01). Conclusion: This study has shown that the dropout rate of treatment in temporomandibular joint disorder is affected by age, sex, distance traveled, occupation, and education.

Alpha-Synuclein Preformed Fibrils Induce Cellular Senescence in Parkinson's Disease Models.

Emerging evidence indicates that cellular senescence could be a critical inducing factor for aging-associated neurodegenerative disorders. However, the involvement of cellular senescence remains unclear in Parkinson's disease (PD). To determine this, we assessed the effects of α-synuclein preformed fibrils (α-syn PFF) or 1-methyl-4-phenylpyridinium (MPP+) on changes in cellular senescence markers, employing α-syn PFF treated-dopaminergic N27 cells, primary cortical neurons, astrocytes and microglia and α-syn PFF-injected mouse brain tissues, as well as human PD patient brains. Our results demonstrate that α-syn PFF-induced toxicity reduces the levels of Lamin B1 and HMGB1, both established markers of cellular senescence, in correlation with an increase in the levels of p21, a cell cycle-arrester and senescence marker, in both reactive astrocytes and microglia in mouse brains. Using Western blot and immunohistochemistry, we found these cellular senescence markers in reactive astrocytes as indicated by enlarged cell bodies within GFAP-positive cells and Iba1-positive activated microglia in α-syn PFF injected mouse brains. These results indicate that PFF-induced pathology could lead to astrocyte and/or microglia senescence in PD brains, which may contribute to neuropathology in this model. Targeting senescent cells using senolytics could therefore constitute a viable therapeutic option for the treatment of PD.

Epstein-Barr Virus Lytic Replication Induces ACE2 Expression and Enhances SARS-CoV-2 Pseudotyped Virus Entry in Epithelial Cells.

Understanding factors that affect the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is central to combatting coronavirus disease 2019 (COVID-19). The virus surface spike protein of SARS-CoV-2 mediates viral entry into cells by binding to the ACE2 receptor on epithelial cells and promoting fusion. We found that Epstein-Barr virus (EBV) induces ACE2 expression when it enters the lytic replicative cycle in epithelial cells. By using vesicular stomatitis virus (VSV) particles pseudotyped with the SARS-CoV-2 spike protein, we showed that lytic EBV replication enhances ACE2-dependent SARS-CoV-2 pseudovirus entry. We found that the ACE2 promoter contains response elements for Zta, an EBV transcriptional activator that is essential for EBV entry into the lytic cycle of replication. Zta preferentially acts on methylated promoters, allowing it to reactivate epigenetically silenced EBV promoters from latency. By using promoter assays, we showed that Zta directly activates methylated ACE2 promoters. Infection of normal oral keratinocytes with EBV leads to lytic replication in some of the infected cells, induces ACE2 expression, and enhances SARS-CoV-2 pseudovirus entry. These data suggest that subclinical EBV replication and lytic gene expression in epithelial cells, which is ubiquitous in the human population, may enhance the efficiency and extent of SARS-CoV-2 infection of epithelial cells by transcriptionally activating ACE2 and increasing its cell surface expression. IMPORTANCE SARS-CoV-2, the coronavirus responsible for COVID-19, has caused a pandemic leading to millions of infections and deaths worldwide. Identifying the factors governing susceptibility to SARS-CoV-2 is important in order to develop strategies to prevent SARS-CoV-2 infection. We show that Epstein-Barr virus, which infects and persists in >90% of adult humans, increases susceptibility of epithelial cells to infection by SARS-CoV-2. EBV, when it reactivates from latency or infects epithelial cells, increases expression of ACE2, the cellular receptor for SARS-CoV-2, enhancing infection by SARS-CoV-2. Inhibiting EBV replication with antivirals may therefore decrease susceptibility to SARS-CoV-2 infection.

Intrasphenoidal Rathke Cleft Cyst: A Rare Case Report.

Rathke cleft cysts are benign lesions of the sellar and suprasellar region. Extrasellar intrasphenoidal Rathke cleft cysts are rare with only one case reported in pediatric age group. The presenting complaints described include headache and diplopia. We report a case of intrasphenoidal Rathke cleft cyst in a 15-year-old girl who presented with headache and visual disturbances. Neuroimaging showed an expansile cystic lesion involving the sphenoid sinus with mass effect over the pituitary and optic chiasma. Endoscopic decompression of the cystic lesion was done and histopathology of the cyst wall revealed it to be Rathke cleft cyst. Follow-up MRI showed total resection of the cystic lesion with residual partial left optic nerve atrophy.

The SUMO Conjugase Ubc9 Protects Dopaminergic Cells from Cytotoxicity and Enhances the Stability of α-Synuclein in Parkinson's Disease Models.

Small ubiquitin-like modifier (SUMO) is a widespread regulatory mechanism of post-translational modification (PTM) that induces rapid and reversible changes in protein function and stability. Using SUMO conjugase Ubc9-overexpressing or knock-down cells in Parkinson's disease (PD) models, we demonstrate that SUMOylation protects dopaminergic cells against MPP+ or preformed fibrils (PFFs) of α-synuclein (α-syn)-induced toxicities in cell viability and cytotoxicity assays. In the mechanism of protection, Ubc9 overexpression significantly suppressed the MPP+ or PFF-induced reactive oxygen species (ROS) generation, while Ubc9-RNAi enhanced the toxicity-induced ROS production. Further, PFF-mediated protein aggregation was exacerbated by Ubc9-RNAi in thioflavin T staining, compared with NC1 controls. In cycloheximide (Chx)-based protein stability assays, higher protein level of α-syn was identified in Ubc9-enhanced green fluorescent protein (EGFP) than in EGFP cells. Since there was no difference in endogenous mRNA levels of α-syn between Ubc9 and EGFP cells in quantitative real-time PCR (qRT-PCR), we assessed the mechanisms of SUMO-mediated delayed α-syn degradation via MG132, proteasomal inhibitor, and PMA, lysosomal degradation inducer. Ubc9-mediated SUMOylated α-syn avoided PMA-induced lysosomal degradation because of its high solubility. Our results suggest that Ubc9 enhances the levels of SUMO1 and ubiquitin on α-syn and interrupts SUMO1 removal from α-syn. In immunohistochemistry, dopaminergic axon tips in the striatum and cell bodies in the substantia nigra from Ubc9-overexpressing transgenic mice were protected from MPTP toxicities compared with wild-type (WT) siblings. Our results support that SUMOylation can be a regulatory target to protect dopaminergic neurons from oxidative stress and protein aggregation, with the implication that high levels of SUMOylation in dopaminergic neurons can prevent the pathologic progression of PD.

Contact Transmission of Vaccinia to an Infant Diagnosed by Viral Culture and Metagenomic Sequencing.

Targeted molecular diagnostic tests and accurate immunoassays have transformed the landscape of clinical virology, calling into question the usefulness of traditional viral culture. Here we present a case where viral culture, followed by metagenomic sequencing, was central to the diagnosis of an unexpected viral infection, with significant clinical and public health implications.

Epstein-Barr virus co-opts TFIIH component XPB to specifically activate essential viral lytic promoters.

Epstein-Barr virus (EBV) is associated with epithelial and lymphoid malignancies, establishes latent infection in memory B cells, and intermittently produces infectious virions through lytic replication. Released virions play a key role in latent reservoir maintenance and transmission. Lytic EBV transcription differs from cellular transcription in requiring a virus-encoded preinitiation complex that binds to TATT motifs unique to EBV late lytic promoters. Expression of 15 late lytic genes that are important for virion production and infectivity is particularly dependent on the EBV SM protein, a nuclear protein expressed early during lytic reactivation that binds to viral RNAs and enhances RNA stability. We recently discovered that spironolactone blocks EBV virion production by inhibiting EBV SM function. Since spironolactone causes degradation of xeroderma pigmentosum group B-complementing protein (XPB), a component of human transcription factor TFIIH, in both B lymphocytes and epithelial cells, we hypothesized that SM utilizes XPB to specifically activate transcription of SM target promoters. While EBV SM has been thought to act posttranscriptionally, we provide evidence that SM also facilitates EBV gene transcription. We demonstrate that SM binds and recruits XPB to EBV promoters during lytic replication. Depletion of XPB protein, by spironolactone treatment or by siRNA transfection, inhibits SM-dependent late lytic gene transcription but not transcription of other EBV genes or cellular genes. These data indicate that SM acts as a transcriptional activator that has co-opted XPB to specifically target 15 EBV promoters that have uniquely evolved to require XPB for activity, providing an additional mechanism to differentially regulate EBV gene expression.

Synergistic Tribo-Activity of Nanohybrids of Zirconia/Cerium-Doped Zirconia Nanoparticles with Nano Lamellar Reduced Graphene Oxide and Molybdenum Disulfide.

Zirconia and 10%, 20%, and 30% cerium-doped zirconia nanoparticles (ZCO), ZCO-1, ZCO-2, and ZCO-3, respectively, were prepared using auto-combustion method. Binary nanohybrids, ZrO2@rGO and ZCO-2@rGO (rGO = reduced graphene oxide), and ternary nanohybrids, ZrO2@rGO@MoS2 and ZCO-2@rGO@MoS2, have been prepared with an anticipation of a fruitful synergic effect of rGO, MoS2, and cerium-doped zirconia on the tribo-activity. Tribo-activity of these additives in paraffin oil (PO) has been assessed by a four-ball lubricant tester at the optimized concentration, 0.125% w/v. The tribo-performance follows the order: ZCO-2@rGO@MoS2 > ZrO2@rGO@MoS2 > ZCO-2@rGO > ZrO2@rGO > MoS2 > ZrO2 > rGO > PO. The nanoparticles acting as spacers control restacking of the nanosheets provided structural augmentation while nanosheets, in turn, prevent agglomeration of the nanoparticles. Doped nanoparticles upgraded the activity by forming defects. Thus, the results acknowledge the synergic effect of cerium-doped zirconia and lamellar nanosheets of rGO and MoS2. There is noncovalent interaction among all the individuals. Analysis of the morphological features of wear-track carried out by scanning electron microscopy (SEM) and atomic force microscopy (AFM) in PO and its formulations with various additives is consistent with the above sequence. The energy dispersive X-ray (EDX) spectrum of ZCO-2@rGO@MoS2 indicates the existence of zirconium, cerium, molybdenum, and sulfur on the wear-track, confirming, thereby, the active role played by these elements during tribofilm formation. The X-ray photoelectron spectroscopy (XPS) studies of worn surface reveal that the tribofilm is made up of rGO, zirconia, ceria, and MoS2 along with Fe2O3, MoO3, and SO42- as the outcome of the tribo-chemical reaction.

Recent Advances in Systems and Network Medicine: Meeting Report from the First International Conference in Systems and Network Medicine.

The First International Conference in Systems and Network Medicine gathered together 200 global thought leaders, scientists, clinicians, academicians, industry and government experts, medical and graduate students, postdoctoral scholars and policymakers. Held at Georgetown University Conference Center in Washington D.C. on September 11-13, 2019, the event featured a day of pre-conference lectures and hands-on bioinformatic computational workshops followed by two days of deep and diverse scientific talks, panel discussions with eminent thought leaders, and scientific poster presentations. Topics ranged from: Systems and Network Medicine in Clinical Practice; the role of -omics technologies in Health Care; the role of Education and Ethics in Clinical Practice, Systems Thinking, and Rare Diseases; and the role of Artificial Intelligence in Medicine. The conference served as a unique nexus for interdisciplinary discovery and dialogue and fostered formation of new insights and possibilities for health care systems advances.

Prevalence of psychological morbidities and their influential variables among nurses in a designated COVID-19 tertiary care hospital in India: A cross-sectional study.

BACKGROUND: Nurses are the main part of the health workforce, performing their duties as frontline warriors against the novel coronavirus pandemic. Nurses involved in the care of infected (COVID-19) patients, may feel more discomfort physically and experience greater psychological morbidities. AIMS AND OBJECTIVES: The main aim of the study is to evaluate the prevalence of anxiety and stress among nurses in a designated COVID-19 hospital and variables that influence these psychological problems. METHODOLOGY: Nurses working in the designated tertiary care hospital were invited to participate in an online cross-sectional survey (dated, September 5-15, 2020). A self-administered questionnaire regarding sociodemographic characteristics, COVID-19-related experiences, perceived threat regarding COVID-19, and two scales (Generalized Anxiety Disorder-7 and Perceived Stress Scale-10) for the assessment of anxiety and stress was applied to nurses. Chi-square test and multiple regression analysis were used to investigate the predictors (risk and protective) of psychological morbidities in nurses. RESULTS: On analysis of 209 participants, it was revealed that 65 (31.1%) participants have anxiety symptoms and 35.40% have moderate to the high level of stress. Being proud of working in this profession was the only protective factor from such psychological morbidities. The identified risk factors for greater anxiety symptoms and moderate-to-high-level stress were, working experience of >10 years (odds ratio [OR] = 3.36), direct involvement in the care of suspected/diagnosed patients (OR = 3.4), feeling worried about being quarantined/isolated (OR = 1.69,) and high risk of being infected at the job (OR = 2.3 for anxiety and OR = 2.1 for moderate-to-high stress). CONCLUSIONS: Deteriorating the psychic health of nurses is one of the major outcomes during the COVID-19 pandemic in India which warrants the necessity of providing psychological support to nurses and controlling the risk factors related to these problems. Greater focus should be on the frontline and experienced nurses.