Ticagrelor alone versus ticagrelor plus aspirin from month 1 to month 12 after percutaneous coronary intervention in patients with acute coronary syndromes (ULTIMATE-DAPT): a randomised, placebo-controlled, double-blind clinical trial.

BACKGROUND: Following percutaneous coronary intervention with stent placement to treat acute coronary syndromes, international clinical guidelines generally recommend dual antiplatelet therapy with aspirin plus a P2Y12 receptor inhibitor for 12 months to prevent myocardial infarction and stent thrombosis. However, data on single antiplatelet therapy with a potent P2Y12 inhibitor earlier than 12 months after percutaneous coronary intervention for patients with an acute coronary syndrome are scarce. The aim of this trial was to assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin, could reduce the incidence of clinically relevant bleeding events without an accompanying increase in major adverse cardiovascular or cerebrovascular events (MACCE). METHODS: In this randomised, placebo-controlled, double-blind clinical trial, patients aged 18 years or older with an acute coronary syndrome who completed the IVUS-ACS study and who had no major ischaemic or bleeding events after 1-month treatment with dual antiplatelet therapy were randomly assigned to receive oral ticagrelor (90 mg twice daily) plus oral aspirin (100 mg once daily) or oral ticagrelor (90 mg twice daily) plus a matching oral placebo, beginning 1 month and ending at 12 months after percutaneous coronary intervention (11 months in total). Recruitment took place at 58 centres in China, Italy, Pakistan, and the UK. Patients were required to remain event-free for 1 month on dual antiplatelet therapy following percutaneous coronary intervention with contemporary drug-eluting stents. Randomisation was done using a web-based system, stratified by acute coronary syndrome type, diabetes, IVUS-ACS randomisation, and site, using dynamic minimisation. The primary superiority endpoint was clinically relevant bleeding (Bleeding Academic Research Consortium [known as BARC] types 2, 3, or 5). The primary non-inferiority endpoint was MACCE (defined as the composite of cardiac death, myocardial infarction, ischaemic stroke, definite stent thrombosis, or clinically driven target vessel revascularisation), with an expected event rate of 6·2% in the ticagrelor plus aspirin group and an absolute non-inferiority margin of 2·5 percentage points between 1 month and 12 months after percutaneous coronary intervention. The two co-primary endpoints were tested sequentially; the primary superiority endpoint had to be met for hypothesis testing of the MACCE outcome to proceed. All principal analyses were assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Sept 21, 2019, and Oct 27, 2022, 3400 (97·0%) of the 3505 participants in the IVUS-ACS study were randomly assigned (1700 patients to ticagrelor plus aspirin and 1700 patients to ticagrelor plus placebo). 12-month follow-up was completed by 3399 (>99·9%) patients. Between month 1 and month 12 after percutaneous coronary intervention, clinically relevant bleeding occurred in 35 patients (2·1%) in the ticagrelor plus placebo group and in 78 patients (4·6%) in the ticagrelor plus aspirin group (hazard ratio [HR] 0·45 [95% CI 0·30 to 0·66]; p<0·0001). MACCE occurred in 61 patients (3·6%) in the ticagrelor plus placebo group and in 63 patients (3·7%) in the ticagrelor plus aspirin group (absolute difference -0·1% [95% CI -1·4% to 1·2%]; HR 0·98 [95% CI 0·69 to 1·39]; pnon-inferiority<0·0001, psuperiority=0·89). INTERPRETATION: In patients with an acute coronary syndrome who had percutaneous coronary intervention with contemporary drug-eluting stents and remained event-free for 1 month on dual antiplatelet therapy, treatment with ticagrelor alone between month 1 and month 12 after the intervention resulted in a lower rate of clinically relevant bleeding and a similar rate of MACCE compared with ticagrelor plus aspirin. Along with the results from previous studies, these findings show that most patients in this population can benefit from superior clinical outcomes with aspirin discontinuation and maintenance on ticagrelor monotherapy after 1 month of dual antiplatelet therapy. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and the Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention in acute coronary syndromes (IVUS-ACS): a two-stage, multicentre, randomised trial.

BACKGROUND: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome. METHODS: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed. FINDINGS: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups. INTERPRETATION: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone. FUNDING: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Chronic cypermethrin induced toxicity and molecular fate assessment within common carp (Cyprinus carpio) using multiple biomarkers approach and its novel therapeutic detoxification.

Cypermethrin (CYP) is a chemical of emerging concern which has persistent and bioaccumulating impacts as it can be found extensively in freshwater ecosystem and agricultural products. It has exposure risk and toxic effects over human edible fish, as common carp. Four groups were designed for toxicity assessment and detoxification approach: control group (CL), CYP exposure group (CYP), CYP + 10% M. oleifera leaves and 10% M. oleifera seeds (CMO group), 10% M. oleifera leaves and 10% M. oleifera seeds (MO group). Trial period was forty days during which cohort of 240 fish in CYP and CMO group was exposed to 1/5 of 96h LC50 of CYP (0.1612 µg/L). CYP-exposed carp exhibited lower growth parameters, but carp fed with 10% M. oleifera seeds and leaves showed significant improvement in growth rate (SGR, RGR) and weight gain (WG) as compared to the control group. CYP exposure negatively affected haemato-biochemical parameters. Moreover, CYP exposure also led to oxidative stress, damaged immunological parameters, genotoxicity and histopathological damage in liver and intestinal cells. Whereas, M. oleifera supplementation has ameliorated these conditions. Thereby, supplementation with M. oleifera is potential and novel therapeutic detoxication approach for common carp and human health against persistent and bioaccumulating emerging chemicals.

Biallelic variants identified in 36 Pakistani families and trios with autism spectrum disorder.

With its high rate of consanguineous marriages and diverse ethnic population, little is currently understood about the genetic architecture of autism spectrum disorder (ASD) in Pakistan. Pakistan has a highly ethnically diverse population, yet with a high proportion of endogamous marriages, and is therefore anticipated to be enriched for biallelic disease-relate variants. Here, we attempt to determine the underlying genetic abnormalities causing ASD in thirty-six small simplex or multiplex families from Pakistan. Microarray genotyping followed by homozygosity mapping, copy number variation analysis, and whole exome sequencing were used to identify candidate. Given the high levels of consanguineous marriages among these families, autosomal recessively inherited variants were prioritized, however de novo/dominant and X-linked variants were also identified. The selected variants were validated using Sanger sequencing. Here we report the identification of sixteen rare or novel coding variants in fifteen genes (ARAP1, CDKL5, CSMD2, EFCAB12, EIF3H, GML, NEDD4, PDZD4, POLR3G, SLC35A2, TMEM214, TMEM232, TRANK1, TTC19, and ZNF292) in affected members in eight of the families, including ten homozygous variants in four families (nine missense, one loss of function). Three heterozygous de novo mutations were also identified (in ARAP1, CSMD2, and NEDD4), and variants in known X-linked neurodevelopmental disorder genes CDKL5 and SLC35A2. The current study offers information on the genetic variability associated with ASD in Pakistan, and demonstrates a marked enrichment for biallelic variants over that reported in outbreeding populations. This information will be useful for improving approaches for studying ASD in populations where endogamy is commonly practiced.

Presence of T3SS (exoS, exoT, exoU and exoY), susceptibility pattern and MIC of MDR-Pseudomonas aeruginosa from burn wounds.

INTRODUCTION: The emergence of resistance is a major public health and clinical issue, particularly in pathogens causing nosocomial infections. Recently, there is the emergence of Pseudomonas aeruginosa resistance to different broad-spectrum antibiotics. METHODOLOGY: The current study was designed to find out the prevalence of multi-drug resistant (MDR) P. aeruginosa in burn patients, the antibiotic susceptibility pattern of MDR Pseudomonas, and to determine the Minimum Inhibitory Concentration (MIC) of the effective antimicrobials. The assessment of virulence genes (exoT, exoS, exoY and exoU) was also achieved through PCR. In the current study wound swabs were collected from 160 burn patients from two burn units (MTI-Govt. Lady Reading Hospital and MTI-Khyber Teaching Hospital). RESULTS: Out of these 160 samples, 26 samples (16.25%) were positive for P. aeruginosa. Per patients, one isolate was included in the current study. Antibiotic susceptibility pattern showed all P. aeruginosa isolates were 100% resistant to amoxicillin-clavulanic acid, 84.62% resistance to Cefepime, and Ceftazidime, and 76.92% resistance to Amikacin, Aztreonam, and Ciprofloxacin. Whereas the lowest resistance was observed to Imipenem and Piperacillin-Tazobactam (53.85%), Colistin Sulfate (23.08%), and Polymyxin-B (15.38%). Regarding the prevalence of MDR, 22 (84.61%) isolates out of 26 were found to be MDR-P. aeruginosa. For MDR-P. aeruginosa, the MIC range was 1-2 µg/mL against Polymyxin-B, 2-8 µg/mL against Colistin sulfate, 16-1024 µg/mL against Imipenem and 128-1024 µg/mL against Piperacillin-Tazobactam. 100% of the isolates carried exoT, 88.46% carried exoY, and 57.69% and 38.46% carried exoU and exoS, respectively. CONCLUSIONS: These findings further emphasize the need for antibiotic discipline and to follow the recommended hospital antibiotic policy to prevent the proliferation of MDR strains of P. aeruginosa in the community.

Motile microorganisms hybrid nanoliquid flow with the influence of activation energy and heat source over a rotating disc.

The present article examines the consequences of a magnetic field, Hall current, and thermal radiation on the spinning flow of hybrid nanofluid (HNF) across a revolving disc. The core objective of the study is to improve the energy transference rate through hybrid nano liquid for industrial and engineering operations. The HNFs have advanced thermophysical characteristics. Therefore, in the current study, a superior class of nanomaterials (carbon nanotubes (CNTs) and Al2O3) are added to the base fluid. The modeled equations are demoted to a dimensionless set of Ordinary differential equations (ODEs) through similarity conversion and are analytically solved by engaging the homotopy analysis method. The physical constraints' effect on energy, velocity, motile microorganism, and mass profiles have been drawn and discussed. For accuracy, the results are compared to the published studies, which ensures the accuracy and reliability of the technique and results. It is observed that the energy communication rate lessens with the flourishing values of thermal radiation and for Hall current. Furthermore, it is noted that due to its carbon-carbon bonding in CNTs, it has a greater tendency for energy propagation than Al2O3nanoparticles.

Formulation and Characterization of Ethyl Cellulose-Based Patches Containing Curcumin-Chitosan Nanoparticles for the Possible Management of Inflammation via Skin Delivery.

Curcumin, a natural phenolic compound, exhibits poor absorption and extensive first pass metabolism after oral administration. In the present study, curcumin-chitosan nanoparticles (cur-cs-np) were prepared and incorporated into ethyl cellulose patches for the management of inflammation via skin delivery. Ionic gelation method was used for the preparation of nanoparticles. The prepared nanoparticles were evaluated for size, zetapotential, surface morphology, drug content, and % encapsulation efficiency. The nanoparticles were then incorporated into ethyl cellulose-based patches using solvent evaporation technique. ATR-FTIR was used to study/assess incompatibility between drug and excipients. The prepared patches were evaluated physiochemically. The in vitro release, ex vivo permeation, and skin drug retention studies were carried out using Franz diffusion cells and rat skin as permeable membrane. The prepared nanoparticles were spherical, with particle size in the range of 203-229 nm, zetapotential 25-36 mV, and PDI 0.27-0.29 Mw/Mn. The drug content and %EE were 53% and 59%. Nanoparticles incorporated patches are smooth, flexible, and homogenous. The in vitro release and ex vivo permeation of curcumin from nanoparticles were higher than the patches, whereas the skin retention of curcumin was significantly higher in case of patches. The developed patches deliver cur-cs-np into the skin, where nanoparticles interact with skin negative charges and hence result in higher and prolonged retention in the skin. The higher concentration of drug in the skin helps in better management of inflammation. This was shown by anti-inflammatory activity. The inflammation (volume of paw) was significantly reduced when using patches as compared to nanoparticles. It was concluded that the incorporation of cur-cs-np into ethyl cellulose-based patches results in controlled release and hence enhanced anti-inflammatory activity.

Cardio protective effect of nicorandil in reperfusion injury among patients undergoing primary percutaneous coronary intervention.

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role.

An Equity-Based Scoring System for Evaluating Surveillance-Related Harm in Public Health Crises.

Background: Although surveillance systems used to mitigate disasters serve essential public health functions, communities of color have experienced disproportionate harms (eg, criminalization) as a result of historic and enhanced surveillance. Methods: To address this, we developed and piloted a novel, equity-based scoring system to evaluate surveillance systems regarding their potential and actual risk of adverse effects on communities made vulnerable through increased exposure to policing, detention/incarceration, deportation, and disruption of access to social services or public resources. To develop the scoring system, we reviewed the literature and surveyed an expert panel on surveillance to identify specific harms (eg, increased policing) that occur through surveillance approaches. Results: Scores were based on type of information collected (individual and/or neighborhood level) and evidence of sharing information with law enforcement. Scores were 0 (no risk of harm identified), 1 (potential for risk), 2 (evidence of risk), and U (data not publicly accessible). To pilot the scoring system, 44 surveillance systems were identified between June 2020 and October 2020 through an environmental scan of systems directly related to COVID-19 (n=21), behavioral and health-related services (n=11), and racism and racism-related factors (n=12). A score of 0-2 was assigned to 91% (n=40) of the systems; 9% were scored U; 30% (n=13) scored a 0. Half scored a 1 (n=22), indicating a "potential for the types of harm of concern in this analysis." "Evidence of harm," a score of 2, was found for 12% (n=5). Conclusions: The potential for surveillance systems to compromise the health and well-being of racialized and/or vulnerable populations has been understudied. This project developed and piloted a scoring system to accomplish this equity-based imperative. The nobler pursuits of public health to improve the health for all must be reconciled with these potential harms.

The Wheat Head Blight Pathogen Fusarium graminearum Can Recruit Collaborating Bacteria from Soil.

In nature, fungal endophytes often have facultative endohyphal bacteria (FEB). Can a model plant pathogenic fungus have them, and does it affect their phenotype? We constructed a growth system/microcosm to allow an F. graminearum isolate to grow through natural soil and then re-isolated it on a gentamicin-containing medium, allowing endohyphal growth of bacteria while killing other bacteria. F. graminearum PH-1 labelled with a His1mCherry gene staining the fungal nuclei fluorescent red was used to confirm the re-isolation of the fungus. Most new re-isolates contained about 10 16SrRNA genes per fungal mCherry gene determined by qPCR. The F. graminearum + FEB holobiont isolates containing the bacteria were sub-cultured several times, and their bacterial contents were stable. Sequencing the bacterial 16SrRNA gene from several Fg-FEB holobiont isolates revealed endophytic bacteria known to be capable of nitrogen fixation. We tested the pathogenicity of one common Fg-FEB holobiont association, F. graminearum + Stenatrophomonas maltophilia, and found increased pathogenicity. The 16SrRNA gene load per fungal His1mCherry gene inside the wheat stayed the same as previously found in vitro. Finally, strong evidence was found for Fg-S. maltophilia symbiotic nitrogen fixation benefitting the fungus.

Coupling phosphate-solubilizing bacteria (PSB) with inorganic phosphorus fertilizer improves mungbean (Vigna radiata) phosphorus acquisition, nitrogen fixation, and yield in alkaline-calcareous soil.

To overcome the problems associated with soil phosphorus (P) insolubility, soil inoculation with phosphate-solubilizing bacteria (PSB) can be used. In a field experiment, we evaluated the efficacy of PSB in enhancing mungbean P acquisition, nitrogen (N) fixation, and morphological and yield traits in alkaline-calcareous soil when added together with P as single superphosphate (SSP) or rock phosphate (RP) at 45 or 90 kg P2O5 ha-1. Coupling PSB with mineral P fertilizers (SSP & RP) improved P use efficiency, mungbean P acquisition, N2 fixation, nodulation, NP uptake, and the morphological and yield-related traits of mungbeans compared with non-fertilized controls and plots received P from mineral sources alone. Soil PSB inoculation with mineral P also improved post-harvest soil fertility relative to pre-harvest by improving soil organic matter from 0.61% to 0.70%, lowering pH from 7.74 to 7.68, and improving soil total N from 0.04 to 0.09%, ABDTPA-extractable P from 2.07 to 3.44 mg kg-1, and potassium (K) concentrations from 100.27 to 129.45 mg kg-1. When combined with PSB, RP generally performed better than SSP. Moreover, there was a significant correlation between soil N and plant N, while the correlation between soil P and plant P was non-significant. The correlation between soil organic matter content and NP uptake by mungbeans was also non-significant. Therefore, adding P as RP at 45-90 kg ha-1, together with PSB inoculation, can be recommended for improving mungbean P acquisition, use efficiency, optimum N2 fixation, and yield in alkaline-calcareous soils.

A case of aortic dissection in familial Mediterranean fever.

Familial Mediterranean fever (FMF) is an ethnicity-specific autoinflammatory disease prevalent in the Arab world. It has various presentations including amyloidosis, small-vessel vasculitis, and pericarditis. Different mutations in the Mediterranean fever (MEFV) gene can cause this disorder and it is inherited in an autosomal recessive pattern. We present a case of a 23-year-old man of Iranian descent with history of periodic fever, diagnosed as Stanford type A aortic dissection secondary to an acute attack of FMF. To the best of our knowledge, this is the first case reported of such a complication. .

Potential cytotoxic and mutagenic effect of Pinus wallichiana, Daphne oleiodes and Bidens chinensis.

The Pinus wallichiana, Daphne oleiodes and Bidens chinensis have a long history of being used traditionally for treatment of various types of disorders. Most of the uses have been without any scientific evidence and toxicological assessment. We evaluated the mutagenic and cytotoxic capabilities of various parts of P. wallichiana, D. oleoides and B. chinensis. Ames Salmonella mutagenicity assay determined the mutagenicity activity against TA 98 and TA 100 bacterial strains of Salmonella typhimurium without metabolic activator S9 system. The number of mutant colonies in negative control was considered as limit to determine the mutagenicity effects of every extract. Brine shrimps lethality bioassay was used to determine the cytotoxic capabilities of the selected plants. The P. wallichiana, D. oleiodes and B. chinensis did not showed any mutagenic activity both for frameshift mutation (TA98) and base-pair substitution (TA100) without S9 mixture. The crude methanolic extract of P. wallichiana stem showed moderate cytotoxicity (53.33%) at 1000 µg/ml with LD50 value 599.634. The D. oleoides fruit showed a toxicity of 60% at 1000 µg/ml with LD50 value 367.730. The B. chinensis (whole plant) showed lethality of 63.3% at 1000 µg/ml, with LD50 204.833. The absence of any mutagenic activity of crude extract of the tested plants in both bacteria strains, TA 98 and TA 100 without the S9 mix confirms the safety of these plants to the consumers.

From Heartbreak to Heart Disease: A Narrative Review on Depression as an Adjunct to Cardiovascular Disease.

Patients with cardiovascular disease (CVD) commonly have subclinical depression and are often delayed in their diagnosis. Literature suggests an increased association of depression and adverse cardiovascular events like myocardial infarction and heart failure. Prevalence of depression in developed countries is approximately 16.6%, and it confers higher cardiovascular mortality even after attrition bias and confounding factors are eliminated. Pharmacological and cognitive-behavioral therapy have been extensively studied, and are generally safe and effective in alleviating depressive symptoms in patients with CVD. However, their impact on cardiovascular outcomes is still unclear. Results of randomized controlled trials have shown antidepressants, especially selective serotonin reuptake inhibitors, to be safe and effective for healing a "broken heart." This review outlines the prevalence of depression in patients with CVD, the pathophysiological mechanism causing cardiovascular events with depression, and a link between depression and CVD. There is a wealth of literature explaining the precursor of CVD in depression, and like all chronic diseases, inflammation seems to be the culprit in this case as well.

Anomalous Behavior Detection Framework Using HTM-Based Semantic Folding Technique.

Upon the working principles of the human neocortex, the Hierarchical Temporal Memory model has been developed which is a proposed theoretical framework for sequence learning. Both categorical and numerical types of data are handled by HTM. Semantic Folding Theory (SFT) is based on HTM to represent a data stream for processing in the form of sparse distributed representation (SDR). For natural language perception and production, SFT delivers a solid structural background for semantic evidence description to the fundamentals of the semantic foundation during the phase of language learning. Anomalies are the patterns from data streams that do not follow the expected behavior. Any stream of data patterns could have a number of anomaly types. In a data stream, a single pattern or combination of closely related patterns that diverges and deviates from standard, normal, or expected is called a static (spatial) anomaly. A temporal anomaly is a set of unexpected changes between patterns. When a change first appears, this is recorded as an anomaly. If this change looks a number of times, then it is set to a "new normal" and terminated as an anomaly. An HTM system detects the anomaly, and due to continuous learning nature, it quickly learns when they become the new normal. A robust anomalous behavior detection framework using HTM-based SFT for improving decision-making (SDR-ABDF/P2) is a proposed framework or model in this research. The researcher claims that the proposed model would be able to learn the order of several variables continuously in temporal sequences by using an unsupervised learning rule.

Optical Coherence Tomography Guidance In The Management Of Acute Coronary Syndrome Based On Plaque Morphology.

BACKGROUND: Acute coronary syndrome (ACS) is one of the leading causes of death worldwide. It is characterized by the formation of coronary artery thrombus which can be either due to plaque rupture, plaque erosion or rupture of a calcific nodule. The aim of study was to assess the plaque morphology leading acute coronary syndrome using OCT and to guide management based on its findings. It was an observational study, conducted at Rawalpindi Institute of Cardiology from Jan to Dec 2019. METHODS: Fifty patients meeting the inclusion criteria were included in the study. OCT procedure was performed following intracoronary injection of 100-150 ug of nitroglycerine. The imaging catheter (OFDI dragon view) of the OCT device (Terumo Luna wave OFDI, Tokyo, Japan) was inserted into the culprit artery. Blood clearance was achieved by injecting diluted iodinated contrast at the rate of 5 ml/sec. Imaging acquisition was obtained following automated pullback at the rate of 25 mm/sec. Pathologies like stent under deployment, mal-apposition, strut fracture, plaque erosion, plaque rupture were assessed by the operating interventionist well versed with the OCT technology and lesion assessment. Data analysis was done using the SPSS version 26. Categorical variables were presented as counts and percentages while continuous variables as mean±SD. RESULTS: A total of 50 patients were included in the study. The mean age was 49.24±11.92. Majority of the patients were male comprising 78.0% of the cases. Plaque rupture was the most common underlying pathology seen in 32.5% of the patients and exclusively in STEMI patients which required stent deployment. Thin cap fibroatheroma was seen in 27.9% of the cases while lipid rich plaque in 23.2% of the cases; again, requiring stent deployment. 9.3% of the cases had plaque erosion while 4.6% had calcific nodule and only 2.3% had intramural hematoma which were treated conservatively. 42.8% of the stent thrombosis patients had under-deployed stents requiring balloon dilatation while 14.2% had mal-apposed stent again requiring balloon dilatation. In contrast 14.2% each had neo-atherosclerosis, stent strut fracture and uncovered stent struts as the underlying pathology for stent thrombosis each requiring stent deployment. CONCLUSIONS: OCT guided PCI in cases of acute coronary syndrome is a valuable modality that gives insight into the underlying pathology of the disease process and also guides in proper management.

Treatment of lymphomas via regulating the Signal transduction pathways by natural therapeutic approaches: A review.

Lymphoma is a heterogeneous group of malignancies, which comprises 4.2 % of all new cancer cases and 3.3 % of all cancer deaths in 2019, globally. The dysregulation of immune system, certain bacterial or viral infections, autoimmune diseases, and immune suppression are associated with a high risk of lymphoma. Although several conventional strategies have improved during the past few decades, but their detrimental impacts remain an obstacle to be resolved. However, natural compounds are considered a good option in the treatment of lymphomas because of their easy accessibility, specific mode of action, high biodegradability, and cost-effectiveness. Vegetables, fruits, and beverages are the primary sources of natural active compounds. The present review investigated the activities of different natural medicinal compounds including curcumin, MK615, resveratrol, bromelain, EGCG, and Annonaceous acetogenins to treat lymphomas. Moreover, in vitro and in vivo studies, classification, risk factors, and diagnosis of lymphoma are also discussed in the present review. The accumulated data proposed that natural compounds regulate the signaling pathways at the level of cell proliferation, apoptosis, and cell cycle to exhibit anti-lymphoma activities both in-vivo and in-vitro studies and suggested that these active compounds could be a good therapeutic option in the treatment of different types of lymphomas.

A Case of Elephantiasis Nostras Verrucosa Secondary to Lymphedema Praecox Complicated by Congestive Cardiac Failure.

BACKGROUND In lymphedema, an imbalance in the formation and absorption of lymph causes accumulation of protein-rich fluid in the interstitium of the most gravity-dependent parts of the body. Diagnosis is usually made based on patient medical history and a physical examination showing a typical appearance of the affected body part. Differential diagnosis is confirmed by imaging. CASE REPORT Primary lymphedema is inherited in through an autosomal dominant pattern. Congestive cardiac failure and non-filarial infections predispose patients to the secondary form of lymphedema, elephantiasis nostras verrucosa (ENV). We present the case of a 65-year-old man with lymphedema praecox complicated by congestive cardiac failure. The patient was experiencing worsening left leg swelling and had a prior history of unilateral leg swelling at puberty. The condition was inherited through an autosomal dominant pattern, as his father, elder brother, and nephew were diagnosed with the same disease. The left leg showed non-pitting edema with indurated, woody skin and lichenification. The right leg had mild pitting edema. There were numerous verrucous folds and cobblestone-like nodules, and plaques and a painless ulcer on the left leg. Laboratory evaluation demonstrated an elevated B-type natriuretic peptide. He was treated with compression stockings and inelastic multi-layer bandaging and was administered limb decongestive treatment. After 1 week of therapy, his swelling had somewhat improved. CONCLUSIONS Various conditions can cause ENV and it can superimpose on any form of hereditary lymphedema. The most effective strategy for this condition seems to be a thorough workup of the underlying cause of the ENV and early intervention.