Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration in older adults: relevance for clinical practice and research.

OBJECTIVE: (1) To compare older adults stratified by supraspinatus tendon tear status (STT status)-no tear (Intact), partial-thickness (PT) tear, full-thickness (FT) tear-by 3D Dixon fat fraction (3D-FF); 2D fat fraction (2D-FF); and 2D Goutallier grade (2D-GG) at the Y-shaped view, and 1.4 cm and 2.8 cm medial to the Y-shaped view. Stratified by STT status to determine (2) correlation of 3D-FF with 2D-FF and 2D-GG and (3) inter-rater reliability at and medial to the Y-shaped view. MATERIALS AND METHODS: Forty-five volunteers ≥ 60 years recruited prospectively received shoulder MRI. 3D-FF and 2D-FF were measured on 6-point-Dixon MRI by three trainees. Goutallier grade was assessed on T1-weighted MRI by three fellowship-trained diagnostic radiologists. Descriptive, reliability, and correlation analyses were performed. RESULTS: Groups showed no difference in age. The FT group showed higher (p < 0.05) mean 3D-FF (14.09% ± 10.99%), mean 2D-FF (1.4 cm medial to Y-shaped view, 14.91% ± 12.11%; 2.8 cm medial to Y-shaped view, 13.32% ± 9.48%), and mean 2D-GG (Y-shaped view, 1.71 ± 0.78; 1.4 cm medial to Y-shaped view, 1.71 ± 0.69; 2.8 cm medial to Y-shaped view, 1.71 ± 0.72), relative to Intact/PT groups. 3D-FF showed strong correlation with 2D-FF among all groups/all analyses (rho, 0.80-0.98; p < 0.001). 3D-FF showed strong correlation with 2D-GG for all FT group analyses (rho, 0.85-0.91; p < 0.05). 3D-FF showed moderate-to-strong correlation considering all Intact/PT group analyses (rho, 0.51-0.79; p < 0.50). Dixon fat fraction showed excellent reliability for all groups (≥ 0.884, intraclass correlation coefficient). Goutallier grade showed excellent reliability for FT group (0.771, weighted Fleiss's kappa) but poor (0.294) and fair (0.502) for Intact and PT groups, respectively. CONCLUSION: Single slice MR image estimation of 3D supraspinatus intramuscular fatty infiltration has merit for continued use in clinical populations requiring potential rotator-cuff-repair surgery. However, Dixon fat fraction should be prioritized for use in research over Goutallier grade due to superior reliability.

An ASER AI/ML expert panel formative user research study for an interpretable interactive splenic AAST grading graphical user interface prototype.

PURPOSE: The AAST Organ Injury Scale is widely adopted for splenic injury severity but suffers from only moderate inter-rater agreement. This work assesses SpleenPro, a prototype interactive explainable artificial intelligence/machine learning (AI/ML) diagnostic aid to support AAST grading, for effects on radiologist dwell time, agreement, clinical utility, and user acceptance. METHODS: Two trauma radiology ad hoc expert panelists independently performed timed AAST grading on 76 admission CT studies with blunt splenic injury, first without AI/ML assistance, and after a 2-month washout period and randomization, with AI/ML assistance. To evaluate user acceptance, three versions of the SpleenPro user interface with increasing explainability were presented to four independent expert panelists with four example cases each. A structured interview consisting of Likert scales and free responses was conducted, with specific questions regarding dimensions of diagnostic utility (DU); mental support (MS); effort, workload, and frustration (EWF); trust and reliability (TR); and likelihood of future use (LFU). RESULTS: SpleenPro significantly decreased interpretation times for both raters. Weighted Cohen's kappa increased from 0.53 to 0.70 with AI/ML assistance. During user acceptance interviews, increasing explainability was associated with improvement in Likert scores for MS, EWF, TR, and LFU. Expert panelists indicated the need for a combined early notification and grading functionality, PACS integration, and report autopopulation to improve DU. CONCLUSIONS: SpleenPro was useful for improving objectivity of AAST grading and increasing mental support. Formative user research identified generalizable concepts including the need for a combined detection and grading pipeline and integration with the clinical workflow.

Estimating 3D supraspinatus intramuscular fatty infiltration in older adults: a pilot study.

BACKGROUND: A recent report suggests that semi-quantitative two-dimensional Goutallier grade (2D-GG) correlates poorly with quantitative three-dimensional Dixon fat fraction (3D-Dixon-FF) on magnetic resonance imaging (MRI). PURPOSE: To determine whether the finding of poor correlation of supraspinatus 3D-Dixon-FF with 2D-GG is reproducible, and to determine the strength of the correlation of 3D-Dixon-FF with quantitative 2D Dixon fat fraction (2D-Dixon-FF). MATERIAL AND METHODS: Ten adults aged ≥60 years were recruited prospectively received shoulder MRI. 2D-Dixon-FF and 3D-Dixon-FF were measured on 6-point Dixon fat fraction maps. 2D-GG was rated on T1-weighted images. RESULTS: The mean age of participants was 70.7 ± 3.7 years. The mean 3D-Dixon-FF was 8.3% ± 5.7%; the mean 2D-Dixon-FF was 7.3% ± 4.4%; and the mean 2D-GG was 0.9 ± 0.7. There was a strong correlation for 3D-Dixon-FF with 2D-Dixon-FF (rho = 0.90; P < 0.001) and with 2D-GG (rho = 0.73; P = 0.017). Excellent inter-observer reliability was found for Dixon fat fraction (intraclass correlation coefficient = 0.946), which was good for Goutallier grade (weighted kappa = 0.634). CONCLUSION: Supraspinatus 3D-Dixon-FF had a strong correlation with 2D-Dixon-FF and 2D-GG in our study population.

Incidental long bone cartilage lesions: is any further imaging workup needed?

OBJECTIVE: To determine the rate of chondrosarcoma in incidentally discovered painless long bone cartilage lesions and to determine if any further imaging is needed. MATERIALS AND METHODS: A cartilage lesion was said to be an enchondroma when it had characteristic matrix mineralization and no aggressive features. Search of all imaging reports and tumor board files for keywords enchondroma, cartilage lesion, chondroid, and chondrosarcoma. Retrospective review of medical records and imaging studies from 4.5-year period. Data points collected included patient age, sex, lesion site, size, symptoms, type of imaging, imaging appearance, and length of follow-up. Only patients with no pain were included as enchondroma. Patients with final diagnosis of chondrosarcoma were included for comparison of all features. RESULTS: Only 1/73 (1.4%) patients with an initial incidentally discovered painless lesion was later diagnosed, with new symptoms, as atypical cartilage tumor. Average age was 59.4 years. Bones involved were the femur (n = 33), humerus (n = 30), tibia (n = 7), fibula (n = 2), and ulna (n = 1). Average enchondroma size was 3.9 cm (range 1.4-11.5). Average follow-up was 47 months (range 2-196 months). Eleven long bone chondrosarcomas were identified. All chondrosarcoma patients had pain and aggressive imaging findings. CONCLUSION: Our study reveals that the rate of chondrosarcoma in incidentally found painless chondroid lesions without aggressive features in long bones is low. Imaging follow-up may be needed only in the setting of new symptoms.

Neuroprotective effects of Bhilawanol and Anacardic acid during glutamate-induced neurotoxicity.

Bhilawanol (Bh) and anacardic acid (AA) are two lipid-soluble compounds mostly found in the nut of Semecarpus anacardium (SA). This herb has many medicinal properties including enhancing learning and memory, yet its active compounds have not been studied for neuroprotective effects. We investigated the neuroprotective effects of Bh and AA against glutamate induced cell death in the adrenal pheochromocytoma cell line of rats (PC12 cells). Cell viability, toxicity and calcium influx were determined by MTT assay, LDH release assay and Fluo-3 imaging while apoptosis was assayed by caspase-3 and Bcl-2 gene expression. Our results showed that Bh and AA treatments significantly increased cell viability, reduced cell toxicity and calcium influx in PC12 cells in addition to suppressing the reactive oxygen species. Furthermore, AA treatment decreased caspase-3 expression level whereas both Bh and AA enhanced the expression of anti-apoptotic gene Bcl-2 in PC12 cells. Both compounds potently inhibited acetylcholinesterase enzyme (AChE) in a dose and time dependent manner. These findings suggest that the traditional use of SA may be explained on the basis of both Bh and AA showing neuroprotective potential due to their effects on enhancing cell viability, reducing cell toxicity most probably by reducing excessive calcium influx and suppression of ROS as well as by decreasing the expression of proapoptotic caspase 3 gene and increasing the expression of antiapoptotic gene Bcl2. Traditional use in enhancing learning and memory was justified in part by inhibition of AChE.

Prevalence of EBV, CMV, and HPV in oral squamous cell carcinoma patients in the Pakistani population.

Many studies have proposed an important role of viruses in the pathogenesis of oral cancer. The present study aimed to find out the prevalence of Epstein-Barr virus (EBV), cytomegalovirus (CMV), and human papillomavirus (HPV) among patients with oral squamous cell carcinoma (OSCC) in a Pakistani cohort. We investigated tissue samples obtained from 58 patients with OSCC using the polymerase chain reaction assay. No sample was positive for HPV. EBV was identified in 15 patients (25.86%), and CMV in three patients (5.17%). Coinfection with one or more viruses was detected in two cases and was coinfection with EBV and CMV. These results suggest a low prevalence of these viruses in OSCC patients in the Pakistani population compared to most other countries where the prevalence of these viruses has been reported in the past. Nevertheless, further studies are necessary to determine the potential role of EBV and the possible importance of CMV as an infection cofactor in oral cancer.

Development of fixed dose combination tablets of aripiprazole plus divalproex sodium and their simultaneous determination using HPLC-UV.

A vast majority of psychiatric patients are effectively treated with combination of drugs to improve efficacy and adherence, but due to limited research and development in fixed dose combination (FDC) in psychiatry, these products are not commonly available. The aim of this study is to prepare cost effective FDC tablets containing aripiprazole and divalproex sodium. Two batches of fixed dose combination tablets, FDC1 and FDC2, were successfully prepared using wet granulation technique. Furthermore, aripiprazole tablets A1 and A2 and divalproex tablets D1 were also formulated as reference to compare the in vitro availability profile. An accurate and simple isocratic HPLC method was established and validated for the simultaneous quantification of aripiprazole and valproic acid in the FDC tablets. A reversed-phase C18 (250 × 4.6 mm) column in isocratic mode was used. The mobile phase consisted of acetonitrile and 0.32% KH2PO4 (60:40, v/v), flow rate was set at 1.0 mL/min and the detection was performed at 210 nm. Average percent recoveries of aripiprazole and valproic acid were 96.0 and 95.5%, respectively, meeting the official requirements. The newly developed FDC product may be used for the better therapeutic outcomes of combined use of aripiprazole and valproic acid, which may improve patient adherence.

Anti-platelet effects of nimesulide in isoproterenol-induced myocardial ischaemia and infarction in rabbits.

BACKGROUND: The present study was designed to determine the effects of cyclooxygenase-2 (COX-2) inhibitor-nimesulide on platelet activating factor (PAF) and arachidonic acid (AA)-induced platelet aggregation during myocardial infarction (Ml) and ischaemia in rabbits. METHODS: Rabbits were divided into three groups; group I served as control and contains normal rabbits that received saline, group II rabbits received saline before induction of Ml, and group Ill rabbits received nimesulide (25 mg/kg) before Ml induction. Myocardial infarction was induced by isoproterenol (ISP) (65 mg/kg) and confirmed by biochemical, electrophysiological and histopathological methods. Platelet aggregation was induced with arachidonic acid (AA) and platelet activating factor (PAF), and monitored by using light transmission aggregometery. RESULTS: When platelets were challenged with two different aggregating agents, nimesulide-treated infarcted rabbits showed resistance to platelet aggregation while non-treated infarcted rabbits were found prone to aggregation with both aggregating agents (P < 0.05). CONCLUSION: These results suggest platelet inhibitory effects of nimesulide during experimental ischaemia and infarction in rabbits.

Multiple pathways are responsible for anti-inflammatory and cardiovascular activities of Hordeum vulgare L.

BACKGROUND: Hordeum vulgare L. (HV or barley) is used by traditional healers to treat various inflammatory and cardiovascular diseases, without the knowledge of pharmacologic rationale behind its actions. This study was designed to explore the potential scientific mechanism(s) that could explain the use of Hordeum vulgare in traditional medicine as a treatment for various inflammatory and cardiovascular diseases. METHODS: A crude extract and its three fractions were prepared from HV and screened for the inhibition of platelet aggregation and various metabolites of cyclooxygenase (COX), lipoxygenase (LOX) pathways of arachidonic acid (AA) metabolism as well as for its effects on certain antioxidant enzymes. Platelet aggregation was monitored using turbidometric principle, AA metabolism through radioimmunoassay and antioxidant enzymes by commercial kits using spectrophotometer. RESULTS: Results show that HV exhibited activities against all human platelet agonists used except adenine diphosphate, and inhibited both COX and LOX pathways of AA metabolism. It also elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). However, these activities were distributed in various fractions of HV. Aqueous fraction was most potent in elevating SOD activity; chloroform fraction had concentrated compounds responsible for COX inhibition while n-hexane seems to possess compounds responsible for LOX inhibition as well as the only fraction enhancing the activity of GPx. CONCLUSIONS: These results suggest the likely mechanisms responsible for observed anti-inflammatory and cardiovascular effects of HV in traditional medicine.

Anti-inflammatory and antiplatelet activities of plasma are conserved across twelve mammalian species.

Human plasma inhibits arachidonic acid metabolism and platelet aggregation. This helps human form a haemostatic control system that prevents the progress of certain aggregatory or inflammatory reactions. Whether this property of plasma is unique to human or extends to other species is not well known. It is speculated that this protective ability of plasma remains evolutionarily conserved in different mammals. In order to confirm this, the effect of plasma from 12 different mammalian species was investigated for its inhibitory potential against arachidonic acid metabolism and platelet aggregation. Metabolism of arachidonic acid by cyclooxygenase and lipoxygenase pathways was studies using radio-immuno assay and thin layer chromatography while platelet aggregation in the plasma of various mammals was monitored following turbedmetric method in a dual channel aggregometer. Results indicate that inhibition of AA metabolism and platelet aggregation is a common feature of plasma obtained from different mammalian species, although there exists large interspecies variation. This shows that besides human, other mammals also possess general protective mechanisms against various aggregatory and inflammatory conditions and this anti-inflammatory property of the plasma is evolutionarily conserved in mammalian species. The most likely candidates responsible for these properties of plasma include haptoglobin, albumin and lipoproteins.

Status of serum adiponectin related to insulin resistance in prediabetics.

UNLABELLED: OBEJCTIVE: To find the status of serum adiponectin in individuals progressing towards Type 2 diabetes mellitus and compare it with normal glucose tolerant subjects to determine the stage where alteration of adiponectin occurred. METHODS: The cross-sectional study was carried out at the Department of Biochemistry, Jinnah Postgraduate Medical Centre, Karachi, during January to August 2008. Subjects were invited through various diabetes screening camps. A total of 608 subjects > or = 30 years of age without prior history of diabetes were screened through fasting plasma glucose and 2-hour oral glucose tolerance test. Forty randomly selected pre-diabetic subjects and 40 age and gender-matched subjects were included in the study. Anthropometric measurements were done. Serum insulin and adiponectin were estimated by enzyme-linked immunosorbent assay. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate insulin resistance mathematically. RESULT: Mean fasting and two-hour plasma glucose, body mass index, waist, hip circumference and blood pressure were significantly raised in pre-diabetics compared to those with normal glucose tolerance. Adiponectin was significantly decreased, while insulin and HOMA-IR were raised significantly in the pre-diabetics. Adiponectin showed significant negative correlation with body mass index (r = -0.31, p = 0.005), fasting plasma glucose (r = -0.24, p = 0.032), 2-hour plasma glucose (r = -0.42, p < 0.0001)), insulin (r = -0.43, p < 0.0001) and HOMA-IR (r = -0.43, p < 0.0001) and remained significant after adjustment of body mass index, gender and insulin level in pre-diabetics. CONCLUSION: Adiponectin estimation may help in earlier identification of impending diabetes. However, casual link between adiponectin and pre-diabetes remained unexplored due to the study design and small sample size that warrants longitudinal large-scale studies.

A review of pomegranate supplementation: A promising remedial avenue for Alzheimer's disease.

Neurodegenerative complications, like Alzheimer's disease (AD) exert adverse effects i.e. psychological and physiological in the central nervous system. The synthetic drugs used for these complications have negative effects on body health and therefore natural remedies are a good and targeted approach to counter such complications. Alternatively, fruits and a variety of biochemicals which are an important source of diet, can be used for remedial purposes. Due to the antioxidant properties of polyphenolic compounds, several companies utilize this property to advertise polyphenol-rich beverages. Pomegranate (Punica granatum L.), is one such fruit that is well known for its medical usage due to its antioxidant properties. In the cuurent study a literature search survey was performed on traditional uses, phytochemicals on pomegranate and their medical applications especaily in neurodegenerative deasese using electronic data bases like PubMed, Google Scholar, Scopus, Science Direct Wikipedia and Springer Nature. Based on previous preclinical and clinical studies, pomegranate juice, extracts, and its bioactive constituents have shown many mitigating properties, including suppression of inflammatory cell signaling, reduction in expression of genes associated with oxidative stress as well as pro-inflammatory cytokines in neurons, decreased production of inflammatory and oxidative stress biomarkers and increased expression of endothelial nitric oxide synthase. It also decreases the expression of soluble amyloid protein procurer ß (sAPPß), ß-secretase and carboxyl terminal fragment ß (CTFß). Similarly, during an in-vivo study on APP/PS1 mice, pomegranate supplementation has been shown to impart cognitive aid by the protection of neurons and triggering neurogenesis through anti-inflammatory signaling pathway. In conclusion, pomegranate supplementation can be a promising source of protection against Alzheimer's disease.

Biocontrol rhizobacteria enhances growth and yield of wheat (Triticum aestivum) under field conditions against Fusarium oxysporum.

The current study aimed to identify the survival of bio-control bacteria with antifungal activity against Fusarium oxysporum and assess their growth promoting activity in wheat crop field conditions. To evaluate the fungicidal activities of isolated bacteria using the dual culture method, both qualitative and quantitative bioassays were performed. Plant Growth Promoting activities such as Indole 3-Acetic Acid (IAA), phosphate solubilization, Hydrogen cyanide (HCN), and Siderophore production were assessed for three biocontrol bacterial isolates (BCB 07, BCB16, and BCB 83) out of 180 with 70% antagonistic activity against Fusarium oxysporum. Chitinase, protease, and cellulase interaction in isolates was also tested. BCB16 was selected as it had 70% antagonist activity against F. oxysporum but also had the highest PGPR (Plant Growth Promoting Rhizobacteria) traits when compared to the other two isolates. BCB16 was also tested for survival in talc powder and in wheat crop field conditions. Even after 4 months in talc powder, the survival rate remained stable. In a wheat crop field, BCB16 reduced the disease incidence of Fusarium oxysporum by 54.38%. When compared to fungus alone treatment, BCB16 increased average yield by 57% alone and 32% in challenged conditions. BCB16 was identified molecularly using the 16s rRNA gene. Bacillus amyloliquefaciens shared 97% of the deduced sequence. The sequence was submitted to genbank and assigned the accession number OM333889. Bacillus amyloliquefaciens has the potential to be used in the field as an alternative to synthetic fungicides against Fusarium oxysporum.

Isolation and characterization of biocontrol bacteria.Molecular Identification of efficient biocontrol bacteria.Survival of biocontrol bacteria in talc powder as carrier material.The Bacillus amyloliquefaciens has plant growth-promoting characteristics.B. amyloliquefaciens reduced the disease incidence of F. oxysporum by 57% in field trials.

Platelet aggregation and anti-inflammatory effects of garden pea, Desi chickpea and Kabuli chickpea.

Inflammation is the natural body defense mechanism for the removal of injurious agents, necrosed cells and tissues from the body. This study was aimed to evaluate the anti-inflammatory and platelet aggregation effects of three medicinal plants of Pakistan. Methanolic extract of garden pea inhibited arachidonic acid (AA)-induced platelet aggregation (IC50 = 35 microg/mL) and platelet activating factor (PAF)-induced platelet aggregation (IC50 = 38 microg/mL) in a dose dependent fashion. Methanolic extract of Desi chickpea inhibited arachidonic acid (AA) induced platelet aggregation (IC50 value = AA = 46 microg/mL) in dose dependent fashion while was found not active against PAF-induced platelet aggregation. Methanolic extract of Kabuli chickpea was found not active against both arachidonic acid (AA)-induced platelet aggregation and PAF-induced platelet aggregation. The best potential to inhibit in vitro COX-2 activity showed garden pea (Pisum sativum: the synthesis of PGE2 reduced by 92% in comparison with untreated control wells) followed by Desi chickpea (Cicer arietinum var; 87% inhibition) and Kabuli chickpea extracts (Cicer arietinum var: 65% inhibition). All extracts were tested at concentration 20 microg/mL. in COX-2 assay. The results indicate that if the same were happening in vito, Garden pea, Desi chickpea and Kabuli chickpea could be useful as natural antithrombotic anti-inflammatory materials.

Report: Platelet aggregation inhibition activity of selected legumes of Pakistan.

The current study was designed to explore the platelet aggregation activity of methanolic extracts of green gram, lentil, mash bean and soya bean. The extracts dose-dependently inhibited platelet aggregation initiated by arachidonic acid (AA) and platelet activating factor (PAF). Extract of green gram was effective only against AA mediated activity while mash bean and soya bean extracts were effective against both AA and PAF mediated activity. But lentil extract has no activity. The order of activity based on IC(50) value is, Mash bean > Soya bean > Green gram. This preliminary result suggests that legume seed extract may be taken as a candidate lead natural compound to be considered in the search for natural products with beneficial effects on aberrant platelet activation mediated cardiovascular disorders.

DNA methylation across the tree of life, from micro to macro-organism.

DNA methylation is a process in which methyl (CH3) groups are added to the DNA molecule. The DNA segment does not change in the sequence, but DNA methylation could alter the action of DNA. Different enzymes like DNA methyltransferases (DNMTs) take part in methylation of cytosine/adenine nucleosides in DNA. In prokaryotes, DNA methylation is performed to prevent the attack of phage and also plays a role in the chromosome replication and repair. In fungi, DNA methylation is studied to see the transcriptional changes, as in insects, the DNA methylation is not that well-known, it plays a different role like other organisms. In mammals, the DNA methylation is related to different types of cancers and plays the most important role in the placental development and abnormal DNA methylation connected with diseases like cancer, autoimmune diseases, and rheumatoid arthritis.

Antiplatelet response to clopidogrel is associated with a haplotype in CYP2C19 gene in Pakistani patients.

Clopidogrel, an antiplatelet drug, is frequently prescribed to patients diagnosed with ischemic diseases such as those suffering from acute coronary syndromes or ischemic stroke. Despite the drug being effective in majority of the patients, some still experience ischemic events early in the treatment which might be due to poor platelet inhibition. This study aims to investigate the association of cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms, haplotypes as well as a wide range of clinical and demographic variables with platelet aggregation phenotypes to clopidogrel in a Pakistani cohort. The study comprised of a total of 120 patients diagnosed with cardiovascular diseases and were treated with clopidogrel. Antiplatelet response to clopidogrel was monitored by Helena AggRAM (HL-2-1785P) and patients with maximal platelet aggregation more than 50% were categorized as low responders and those with less than 50% as high responders. Our results show that 56.6% of patients were homozygous for the CYP2C19 wild-type allele, 38.3% of patients possessed one copy of the CYP2C19*2 allele and 5% of patients possessed both CYP2C19*2 alleles. No CYP2C19*3 allele was found in our patient cohort. There was no statistically significant difference between the high and low responder groups to clopidogrel in terms of extensive, intermediate and poor metabolizer genotypes. However, haplotype (H1), leukocyte count, random blood glucose, and history of diabetes mellitus was associated with the antiplatelet response to clopidogrel. The prevalence of clopidogrel resistance in our population was in line with that reported for other regional and global populations.

Deciphering SARS CoV-2-associated pathways from RNA sequencing data of COVID-19-infected A549 cells and potential therapeutics using in silico methods.

BACKGROUND: Coronavirus (CoV) disease (COVID-19) identified in Wuhan, China, in 2019, is mainly characterized by atypical pneumonia and severe acute respiratory syndrome (SARS) and is caused by SARS CoV-2, which belongs to the Coronaviridae family. Determining the underlying disease mechanisms is central to the identification and development of COVID-19-specific drugs for effective treatment and prevention of human-to-human transmission, disease complications, and deaths. METHODS: Here, next-generation RNA sequencing (RNA Seq) data were obtained using Illumina Next Seq 500 from SARS CoV-infected A549 cells and mock-treated A549 cells from the Gene Expression Omnibus (GEO) (GSE147507), and quality control (QC) was assessed before RNA Seq analysis using CLC Genomics Workbench 20.0. Differentially expressed genes (DEGs) were imported into BioJupies to decipher COVID-19 induced signaling pathways and small molecules derived from chemical synthesis or natural sources to mimic or reverse COVID -19 specific gene signatures. In addition, iPathwayGuide was used to identify COVID-19-specific signaling pathways, as well as drugs and natural products with anti-COVID-19 potential. RESULTS: Here, we identified the potential activation of upstream regulators such as signal transducer and activator of transcription 2 (STAT2), interferon regulatory factor 9 (IRF9), and interferon beta (IFNß), interleukin-1 beta (IL-1ß), and interferon regulatory factor 3 (IRF3). COVID-19 infection activated key infectious disease-specific immune-related signaling pathways such as influenza A, viral protein interaction with cytokine and cytokine receptors, measles, Epstein-Barr virus infection, and IL-17 signaling pathway. Besides, we identified drugs such as prednisolone, methylprednisolone, diclofenac, compound JQ1, and natural products such as Withaferin-A and JinFuKang as candidates for further experimental validation of COVID-19 therapy. CONCLUSIONS: In conclusion, we have used the in silico next-generation knowledge discovery (NGKD) methods to discover COVID-19-associated pathways and specific therapeutics that have the potential to ameliorate the disease pathologies associated with COVID-19.

Supraspinatus fatty infiltration on MRI among older adults receiving physical therapy as initial management for clinically suspected rotator cuff tear: A pilot study.

Objectives: Rotator cuff (RC) tear is common among adults ≥60 years, with supraspinatus tear most common. Intramuscular fatty infiltration (FI) on imaging is predictive of long-term outcomes following RC tear. Physical therapists routinely diagnose RC tear only by clinical examination since most do not order imaging studies. Thus, there is limited knowledge about FI in older populations receiving physical therapy (PT) for initial management of RC tear. The primary objective of our pilot study is to determine longitudinal differences in supraspinatus FI over time among older adults receiving PT (PT cohort) for initial management of RC tear relative to older adult volunteers (control cohort), and with secondary objective to evaluate longitudinal self-reported shoulder function over time. Material and Methods: This was a prospective longitudinal cohort study. Forty adults, 60-85 years, were enrolled at baseline; one follow-up visit at ≥6 months. Shoulder magnetic resonance imaging and clinical screening for Charlson comorbidity index (CCI), body mass index (BMI), and American Shoulder and Elbow Surgeon (ASES) score were completed at baseline and follow-up visits. Supraspinatus FI was evaluated by 6-point Dixon fat fraction and Goutallier grade. PT (n = 15) and control (n = 25) cohorts were stratified by supraspinatus status: Intact (no tear), partial-thickness tear (PTT), and full-thickness tear (FTT). Comparisons within cohort were performed by Kruskal-Wallis test and between cohorts by Mann-Whitney U-test. Interobserver reliability was performed for Dixon fat fraction and Goutallier grade. Results: PT cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for FTT by Goutallier grade (no tear, 0.5 ± 0.5; PTT, 1.1 ± 0.2; and FTT, 1.5 ± 0.5; P = 0.033) and by Dixon fat fraction (no tear, 4.6% ± 1.4%; PTT, 6.1% ± 1.9%; and FTT, 6.7% ± 2.5%; P = 0.430). Control cohort at baseline showed no difference for age, BMI, CCI, and ASES score; supraspinatus FI was highest for supraspinatus FTT by Dixon fat fraction (no tear, 5.8% ± 1.2%; PTT, 7.1% ± 6.3%; and FTT, 21.4% ± 10.4%; P = 0.034) and by Goutallier grade (no tear, 0.8 ± 0.5; PTT, 1.0 ± 0.6; and FTT, 2.4 ± 1.7; P = 0.141). No difference between similar PT and control cohort subgroups at baseline except no tear groups for ASES score (PT cohort, 58.9 ± 8.2; control cohort, 84.0 ± 21.9; P = 0.049). No differences were identified for Δ-Dixon fat fraction and Δ-Goutallier grade over time in the PT and control cohorts. PT cohort no tear subgroup showed significant improvement (P = 0.042) for Δ-ASES score over time relative to PTT and FTT subgroups; no difference for Δ-ASES score over time in the control cohort. Conclusion: Full-thickness RC tear showed higher levels of FI relative to PTT or no tear at baseline. Our pilot study's trend suggested that older adults receiving PT for initial management of RC tear have full-thickness RC tear for shorter duration based on relative lower levels of FI at baseline as compared to older adult volunteers with full-thickness RC tear. Our pilot study also found that older adults in the PT cohort with no tear had superior shoulder functional recovery by ASES score over time relative to full-thickness and PTTs.

A Review on Therapeutic Potential of Natural Phytocompounds for Stroke.

Stroke is a serious condition that results from an occlusion of blood vessels that leads to brain damage. Globally, it is the second highest cause of death, and deaths from strokes are higher in older people than in the young. There is a higher rate of cases in urban areas compared to rural due to lifestyle, food, and pollution. There is no effective single medicine for the treatment of stroke due to the multiple causes of strokes. Thrombolytic agents, such as alteplase, are the main treatment for thrombolysis, while multiple types of surgeries, such ascraniotomy, thrombectomy, carotid endarterectomy, and hydrocephalus, can be performed for various forms of stroke. In this review, we discuss some promising phytocompounds, such as flavone C-glycoside (apigenin-8-C-ß-D-glucopyranoside), eriodictyol, rosamirinic acid, 6″-O-succinylapigenin, and allicin, that show effectiveness against stroke. Future study paths are given, as well as suggestions for expanding the use of medicinal plants and their formulations for stroke prevention.