Pharmacogenomics driven decision support prototype with machine learning: A framework for improving patient care.

Introduction: A growing number of healthcare providers make complex treatment decisions guided by electronic health record (EHR) software interfaces. Many interfaces integrate multiple sources of data (e.g., labs, pharmacy, diagnoses) successfully, though relatively few have incorporated genetic data. Method: This study utilizes informatics methods with predictive modeling to create and validate algorithms to enable informed pharmacogenomic decision-making at the point of care in near real-time. The proposed framework integrates EHR and genetic data relevant to the patient's current medications including decision support mechanisms based on predictive modeling. We created a prototype with EHR and linked genetic data from the Department of Veterans Affairs (VA), the largest integrated healthcare system in the US. The EHR data included diagnoses, medication fills, and outpatient clinic visits for 2,600 people with HIV and matched uninfected controls linked to prototypic genetic data (variations in single or multiple positions in the DNA sequence). We then mapped the medications that patients were prescribed to medications defined in the drug-gene interaction mapping of the Clinical Pharmacogenomics Implementation Consortium's (CPIC) level A (i.e., sufficient evidence for at least one prescribing action) guidelines that predict adverse events. CPIC is a National Institute of Health funded group of experts who develop evidence based pharmacogenomic guidelines. Preventable adverse events (PAE) can be defined as a harmful outcome from an intervention that could have been prevented. For this study, we focused on potential PAEs resulting from a medication-gene interaction. Results: The final model showed AUC scores of 0.972 with an F1 score of 0.97 with genetic data as compared to 0.766 and 0.73 respectively, without genetic data integration. Discussion: Over 98% of people in the cohort were on at least one medication with CPIC level a guideline in their lifetime. We compared predictive power of machine learning models to detect a PAE between five modeling methods: Random Forest, Support Vector Machine (SVM), Extreme Gradient Boosting (XGBoost), K Nearest neighbors (KNN), and Decision Tree. We found that XGBoost performed best for the prototype when genetic data was added to the framework and improved prediction of PAE. We compared area under the curve (AUC) between the models in the testing dataset.

Thymoquinone supplementation mitigates arsenic-induced cytotoxic and genotoxic alterations in rat liver.

Arsenic, a widespread environmental toxin, produces multiple organ toxicity, including hepatotoxicity. Thymoquinone (TQ) is known to restore liver functions in several hepatic injury models. This study aims to assess the mitigative potential of TQ against sodium arsenate (NaAs)-induced cytotoxic and genotoxic alterations in the liver. Rats were randomly distributed to control, NaAs, TQ, and NaAs+TQ groups. NaAs+TQ and TQ group of rats were pre-treated with TQ (1.5 mg/kg bwt, orally) for 14 days, and the treatment was further continued for 30 days, with and without NaAs treatment (5 mg/kg bwt, orally), respectively. The deleterious histological alterations in the liver of arsenic intoxicated animals were accompanied by an upsurge in the activities of serum ALT and AST, the diagnostic indicators of liver injury. NaAs caused pronounced alterations in the activities of membrane marker and carbohydrate metabolic enzymes and the enzymatic and non-enzymatic components of hepatic antioxidant defense. Significant hepatocyte DNA damage and hepatic arsenic accumulation were also observed in arsenic-exposed rats. TQ supplementation alleviated these adverse alterations and improved the overall hepatic metabolic and antioxidant status in NaAs-administered rats. Prevention of oxidative injury could be the key mechanism of TQ-elicited protective effects. TQ may have an excellent scope as a dietary supplement in the management of arsenic-induced hepatic pathophysiology.

Light and scanning electron microscopic comparative studies of geminivirus infected and healthy Eclipta alba (L.).

Eclipta alba (L.) is a valuable medicinal plant. However, its medicinal efficacy can be affected by geminivirus infection. Therefore, identification of healthy specimen is essential before to use as medicine. The present study provided the taxonomic characterization of geminivirus infected and healthy E. alba plant by studying apparent morphology and microscopic features through light and scanning electron microscopy. Before taxonomic characterization infected and healthy specimens were separated through molecular detection of geminivirus. Results of morphological studies reported that geminivirus infected E. alba plant showed systematic symptoms of infection like stunted growth, distortion and chlorosis of leaves, decrease in size of root, shoot and fruit, and so forth in comparison to healthy specimen. Anatomical findings reported that in both plants anomocytic and anisocytic types of stomata with multicellular warty trichomes were present. However, variations were observed in quantitative measures such as size of trichomes, epidermal, subsidiary and guard cells. Palynological observations identifies that both plants possessed tricolporate type of pollen but variation was mainly observed in size and shape of pollen, thickness of exine and intine, P/E ratio, pore size, interspecific difference, size of colpi, and pollen ornamentation. Overall this study concluded that both healthy and infected E. alba do not reported much variations in qualitative taxonomic features, but can be differentiated in terms of quantitative taxonomic evidences. Future studies are recommended for pharmacological analysis of both healthy and virus infected plants. RESEARCH HIGHLIGHTS: Eclipta alba has incredible therapeutic worth, but due to geminivirus infection the plant is affecting badly. Hence, the present studies give a comprehensive taxonomic report on the geminivirus infected and healthy plant species.

Morphological and palynological assessment of taxonomically problematic genus Paspalum based on light and scanning electron microscopy.

Present research work was carried out to clarify the variations among species of genus Paspalum morphologically and palynologically as this genus is taxonomically difficult due to having multiple similar morphologically overlapping characters which make it difficult to identify. Henceforth present research work was carried out to delimit taxa within the same genus by morphological and palynological tools through light microscopy (LM) and scanning electron microscopy (SEM). Both these tools are considered as the most useful taxonomic characters for taxonomically problematic genera. The results showed a lot of variations among morphological characters. In Paspalum dilatatum, the upper glume was ovate whereas in the other two species, the upper glume was elliptic. The upper glume apex found in P. dilatatum and Paspalum scrobiculatum was obtuse whereas in Paspalum distichum, upper glume apex was acute. Glume nerves showed variation in all three species. Paspalum distichum was 3 nerved, P. scrobiculatum was 5-7 nerved, and P. dilatatum was 5-9 nerved. All three species showed variation in lemma nerves. Paspalum scrobiculatum had 3 nerved lemma whereas in P. distichum 3-5 nerved and P. dilatatum 5-9 nerved lemma were present. In polar and equatorial view, pollen grains ranged from 25 (20-30) to 37.5 (30-45) µm. Paspalum distichum appeared to be the smallest in size whereas P. dilatatum was the largest. Exine thickness ranged from 0.75 (0.5-1) to 1.35 (1.2-1.5) µm. The higher value of pollen fertility was found in P. scrobiculatum as 87.69% and the lowest value was in P. distichum as 78.08%. Morphological keys were also given for correct identification.

Morphological and palynological assessment of some taxa of genus Echinochloa through light and scanning electron microscopy.

The present study was undertaken to gather information on selected species of Echinochloa based on their morphological and palyonological examination through light and scanning electron microscopy. As the Echinochloa species are most problematic grass weeds and exhibit high interspecific and intraspecific variability so due to their great morphological diversity it is difficult to recognize them. A lot of variation was observed in morphological features of studied taxa. In the present study, E. colona had more or less spreading dense racemes whereas in E. crus-galli racemes were linear to ovate. Upper glume surface was pubescent in E. colona, hispid in E. crus-galli and spinose in E. walteri. E. colona was comprised of five-nerved glumes whereas in E. crus-galli glumes were three-nerved. Although pollen basic characters in family Poaceae remains consistent but great variation was observed in pollen of studied taxa. The pollen size was quite variable among the species of genus Echinochloa. In polar view, the size of pollen grains ranged from 27.5 (20-35) µm to 40 (30-50) µm. E. crus-galli was appeared to be the smallest in size whereas E. colona was the largest.). P/E ratio ranged from 0.84 to 1.15 µm among the species. The highest value of pollen fertility was found in E. colona as 93.33% and lowest was in E. crus-galli as 87.50%. The morphological key of studied taxa is also given to study variations. In conclusion, it was observed that microscopy of morphological and palynological assessment can play a vital role in identification of taxonomically problematic taxa.

Oral Nigella sativa oil administration alleviates arsenic-induced redox imbalance, DNA damage, and metabolic and histological alterations in rat liver.

Arsenic, an omnipresent environmental contaminant, is regarded as a potent hepatotoxin. Nigella sativa oil (NSO) consumption has been shown to improve hepatic functions in various in vivo models of acute hepatic injury. The present study evaluates the protective efficacy of NSO against sodium arsenate (As)-induced deleterious alterations in the liver. Male Wistar rats were divided into four groups, namely, control, As, NSO, and AsNSO. After pre-treating rats in AsNSO and NSO groups with NSO (2 mL/kg bwt, orally) for 14 days, NSO treatment was further extended for 30 days, with and without As treatment (5 mg/kg bwt, orally), respectively. As induced an upsurge in serum ALT and AST activities indicating liver injury, as also confirmed by the histopathological findings. As caused significant alterations in the activities of membrane marker enzymes and carbohydrate metabolic enzymes, and in the vital components of antioxidant defense system. Marked DNA damage and hepatic arsenic accumulation were also observed in As-treated rats. Oral NSO administration ameliorated these deleterious alterations and improved overall hepatic antioxidant and metabolic status in As-treated rats. Prevention of oxidative damage could be the underlying mechanism of NSO-mediated protective effects. The results suggest that NSO could be a useful dietary supplement in the management of arsenic hepatotoxicity.

Application of multimicroscopic techniques (LM and SEM) in comparative palynological study of Asteroideae members, inhabited in Pakistan.

In the present study light and scanning electron microscopic approaches were used to study the palynological variations among 30 Asteroideae members. Variety of qualitative and quantitative palynological characters like pollen shape and type, pollen sculpturing, pollen size, P/E ratio, exine and intine thickness, interspecific difference, colpi size, pore size, spines length, spine width, and pollen fertility were observed. Results reported remarkable variations among pollen characters of studied taxa. The shape of pollen grains in polar and equatorial views varied from specie to specie such as spheroidal, prolate, oblate, subspheroidal, oblate spheroidal, prolate spheroidal, suboblate, and sub prolate. Bidens pilosa L. showed maximum pollen size in both polar and equatorial views, whereas minimum pollen size in polar view was found in Tetraneuris scaposa (DC.) Greene. (i.e., 30.5 µm) and in equatorial view was found in Cosmos sulphureus Cav. (25.5 µm).The highest P/E ratio (1.39 µm) was measured in Glebionis coronaria L. The values of exine and intine thickness also varied. Tricolporate, tetracolporate, trizonocolporate, pentoporate, and polypentoporate pollen types were examined. Spinateand echinate pollen sculpturingobserved under SEM. Variations in spine length and width also recorded. The maximum pollen fertility (98%) was measured in Chrysanthemum morifolium Ramat. and the lowest (56%) was recorded in Thymophylla tenuiloba (DC.) Small. It was concluded that the variations in qualitative and quantitative characters were seemed to be valuable for the taxonomic investigations of Asteroideae taxa.

Pollen morphological assessment of specific selected species of district Sheikhupura, Punjab, Pakistan under LM and SEM.

Around 30 pollen samples, 16 families and 25 genera that were gathered, identified and preserved from 6 different localities of District Sheikhupura. Light and scanning electron microscopy was done for all collected flora. Out of the total samples, 43% specie was identified as herbs, 23% as shrubs, and 33% were identified as trees. The flora was both wild and cultivated. Wild plants were 33%, cultivated 40% and 26% of them were both wild and cultivated. Qualitative and Quantitative survey of pollens revealed polar shape of pollens were 37% spheroidal, 20% prolate spheroidal, 17% oblate spheroidal, remaining were rectangular and pecolpate. Sexine and nexine were available in 100% of samples. Thirty-three percentage of pollen grains were having spines on them. The presence of spines on pollen grains represents the evolutionary relationship amongst the plants. Current study was conducted to record and analyze palynomorphic diversity in district Sheikhupura, Punjab, Pakistan.

Scanning Electron Microscopy-based palynological characterization of selected Euphorbiaceae taxa colonized in Pakistan.

The present study was carried out on scanning electron microscopic-based palynological characterization of selected 20 Euphorbiaceae taxa. In this study, important pollen qualitative and quantitative features of selected Euphorbiaceae species such as polar diameter, equatorial diameter, P/E ratio, sculpturing of pollen, exine thickness, intine thickness, presence or absence of colpi and length of colpi, and pollen fertility were examined. Remarkable variations in these pollen characters had been observed among these species. In both polar and equatorial views, Riccinus communis L. exhibited the highest pollen size (polar = 264.1 µm, Equatorial = 270 µm), while Acalypha wilkesiana Mull Arg. showed lowest pollen size (Polar = 17 µm, Equatorial = 18.5 µm). Most of the pollen varied from oblate to spheroidal in shape. With regard to the P/E ratio, Sapium sebiferum L. Roxb showed the highest ratio while Bischofia javanica Blume showed minimum, that is, 1.18 and 0.85, respectively. Intine and exine thickness also varied. Most of the pollen grains were monade. Tricolporate, tricolpate, monocolpate, pentaporate, and polyporate pollen aperture types have been observed. Most of the plants showed regular, reticulate, and echinate pollen sculpturing. Pollen fertility also varied from species to species but most of the plant showed pollen fertility between 70 and 80%. Through this work, it has been concluded that quantitative and qualitative pollen features are helpful at the specific level as well as the generic level and can provide a fruitful taxonomic solution.

Scanning electron microscopic screening; Can it be a taxonomic tool for identification of traditional therapeutic plants.

The limiting factor in the utilization of herbal medicine is the risk of replacement or substitution of their plant resources. Therefore, the authentication of medicinal plants before its use in herbal medicines is essentially required. Hence, the prime objective of this study was to provide some reliable morpho-anatomical and morpho-palynological tools for the identification of nine traditional therapeutic plants of district Lahore. For this study, scanning electron microscopic and light microscopic approaches has been employed. Results reported great variations in qualitative and quantitative morpho-anatomical features of the epidermal cell, stomatal complexes, trichomes, silica bodies and oil droplets. For example, Aegle marmelos L. can be distinguished from Cestrum diurnum L. based on epidermal cell shapes, as irregular cells in former and lobed cells shape in later one. Similarly unicellular, bicellular, and multicellular trichomes could be an identification basis for Cynodon dactylon L., Lantana camara L., and Pongamia pinnata L., respectively. In combination with these morpho-anatomical characters, SEM-based morpho-palynological characterization also reported diagnostic value. Both the Aegle marmelos and Lantana camara possessed similar cell shape (irregular) but can be delimited based on their pollen morphology as spheroidal pollen was reported in Aegle marmelos whereas prolate in Lantana camara. Moreover, quantitative characters also aid well for species delimitation, such as prolate pollen found in both Cestrum diurnum and Terminalia chebula Retz. but both of these varied in their P/E ratio, that is, 0.97 and 0.88, respectively. The leaf epidermal characters in correlation with morph-palynological traits showed potential for taxonomic resolution at the species level. RESEARCH HIGHLIGHTS: This study provides valuable morpho-anatomical and morpho-palynological tools for the nine traditional therapeutic plants of the district, Lahore, Pakistan. Light and scanning electron microscopic studies provided useful systematic data for the identification of studied plants. This systematic data include moprho-anatomical and morpho-palynological keys for the studied plants. This data can be used for future identification purposes.

Early initiation of prophylactic anticoagulation for prevention of COVID-19 mortality: a nationwide cohort study of hospitalized patients in the United States.

IMPORTANCE: Deaths among patients with coronavirus disease 2019 (COVID-19) are partially attributed to venous thromboembolism and arterial thromboses. Anticoagulants prevent thrombosis formation, possess anti-inflammatory and anti-viral properties, and may be particularly effective for treating patients with COVID-19. OBJECTIVE: To evaluate whether initiation of prophylactic anticoagulation within 24 hours of admission is associated with decreased risk of death among patients hospitalized with COVID-19. DESIGN: Observational cohort study. SETTING: Nationwide cohort of patients receiving care in the Department of Veterans Affairs, the largest integrated healthcare system in the United States. PARTICIPANTS: All patients hospitalized with laboratory-confirmed SARS-CoV-2 infection March 1 to July 31, 2020, without a history of therapeutic anticoagulation. EXPOSURES: Prophylactic doses of subcutaneous heparin, low-molecular-weight heparin, or direct oral anticoagulants. MAIN OUTCOMES AND MEASURES: 30-day mortality. Secondary outcomes: inpatient mortality and initiating therapeutic anticoagulation. RESULTS: Of 4,297 patients hospitalized with COVID-19, 3,627 (84.4%) received prophylactic anticoagulation within 24 hours of admission. More than 99% (n=3,600) received subcutaneous heparin or enoxaparin. We observed 622 deaths within 30 days of admission, 513 among those who received prophylactic anticoagulation. Most deaths (510/622, 82%) occurred during hospitalization. In inverse probability of treatment weighted analyses, cumulative adjusted incidence of mortality at 30 days was 14.3% (95% CI 13.1-15.5) among those receiving prophylactic anticoagulation and 18.7% (95% CI 15.1-22.9) among those who did not. Compared to patients who did not receive prophylactic anticoagulation, those who did had a 27% decreased risk for 30-day mortality (HR 0.73, 95% CI 0.66-0.81). Similar associations were found for inpatient mortality and initiating therapeutic anticoagulation. Quantitative bias analysis demonstrated that results were robust to unmeasured confounding (e-value lower 95% CI 1.77). Results persisted in a number of sensitivity analyses. CONCLUSIONS AND RELEVANCE: Early initiation of prophylactic anticoagulation among patients hospitalized with COVID-19 was associated with a decreased risk of mortality. These findings provide strong real-world evidence to support guidelines recommending the use of prophylactic anticoagulation as initial therapy for COVID-19 patients upon hospital admission.

Synthesis, ADMET prediction and reverse screening study of 3,4,5-trimethoxy phenyl ring pendant sulfur-containing cyanopyrimidine derivatives as promising apoptosis inducing anticancer agents.

Cancer remains considered as one of the leading global health problems either due to meagre and suboptimal therapeutic response of chemotherapeutic agents or due to the emergence of spontaneous complex multidrug resistance in cancer cells. This created a persistent need for the development of new anticancer agents. Enthralled by the high success rate for natural product-based drug discovery and current research scenario, we synthesized a new series of 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivatives clubbed with different amines intending to search an anticancer lead compound. To probe the anti-proliferative spectrum of the synthesized derivatives, an in-vitro evaluation was piloted against a panel of 60 cancer cell lines at the National Cancer Institute (NCI) representing major types of cancer diseases. Most of the derivatives showed good to moderate anti-proliferative activity. The results revealed that compound 4e displayed the most promising broad-spectrum anticancer activity with high growth inhibition of various cell lines representing multiple cancers diseases. Mechanistic investigation of compound 4e in human breast cancer MDA-MB-231 cells showed that compound 4e triggers cell death through the induction of apoptosis. ADMET studies and reverse screening were also performed to identify the potential targets of designed molecules. It was concluded that 3,4,5-trimethoxy phenyl ring pendant sulfur-containingcyanopyrimidine derivative 4e could act as a promising hit molecule for further development of novel anticancer therapeutics.

Patterns of COVID-19 testing and mortality by race and ethnicity among United States veterans: A nationwide cohort study.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19). We investigated racial and ethnic disparities in patterns of COVID-19 testing (i.e., who received testing and who tested positive) and subsequent mortality in the largest integrated healthcare system in the United States. METHODS AND FINDINGS: This retrospective cohort study included 5,834,543 individuals receiving care in the US Department of Veterans Affairs; most (91%) were men, 74% were non-Hispanic White (White), 19% were non-Hispanic Black (Black), and 7% were Hispanic. We evaluated associations between race/ethnicity and receipt of COVID-19 testing, a positive test result, and 30-day mortality, with multivariable adjustment for a wide range of demographic and clinical characteristics including comorbid conditions, health behaviors, medication history, site of care, and urban versus rural residence. Between February 8 and July 22, 2020, 254,595 individuals were tested for COVID-19, of whom 16,317 tested positive and 1,057 died. Black individuals were more likely to be tested (rate per 1,000 individuals: 60.0, 95% CI 59.6-60.5) than Hispanic (52.7, 95% CI 52.1-53.4) and White individuals (38.6, 95% CI 38.4-38.7). While individuals from minority backgrounds were more likely to test positive (Black versus White: odds ratio [OR] 1.93, 95% CI 1.85-2.01, p < 0.001; Hispanic versus White: OR 1.84, 95% CI 1.74-1.94, p < 0.001), 30-day mortality did not differ by race/ethnicity (Black versus White: OR 0.97, 95% CI 0.80-1.17, p = 0.74; Hispanic versus White: OR 0.99, 95% CI 0.73-1.34, p = 0.94). The disparity between Black and White individuals in testing positive for COVID-19 was stronger in the Midwest (OR 2.66, 95% CI 2.41-2.95, p < 0.001) than the West (OR 1.24, 95% CI 1.11-1.39, p < 0.001). The disparity in testing positive for COVID-19 between Hispanic and White individuals was consistent across region, calendar time, and outbreak pattern. Study limitations include underrepresentation of women and a lack of detailed information on social determinants of health. CONCLUSIONS: In this nationwide study, we found that Black and Hispanic individuals are experiencing an excess burden of SARS-CoV-2 infection not entirely explained by underlying medical conditions or where they live or receive care. There is an urgent need to proactively tailor strategies to contain and prevent further outbreaks in racial and ethnic minority communities.

Covid-19 by Race and Ethnicity: A National Cohort Study of 6 Million United States Veterans.

BACKGROUND: There is growing concern that racial and ethnic minority communities around the world are experiencing a disproportionate burden of morbidity and mortality from symptomatic SARS-Cov-2 infection or coronavirus disease 2019 (Covid-19). Most studies investigating racial and ethnic disparities to date have focused on hospitalized patients or have not characterized who received testing or those who tested positive for Covid-19. OBJECTIVE: To compare patterns of testing and test results for coronavirus 2019 (Covid-19) and subsequent mortality by race and ethnicity in the largest integrated healthcare system in the United States. DESIGN: Retrospective cohort study. SETTING: United States Department of Veterans Affairs (VA). PARTICIPANTS: 5,834,543 individuals in care, among whom 62,098 were tested and 5,630 tested positive for Covid-19 between February 8 and May 4, 2020. Exposures: Self-reported race/ethnicity. MAIN OUTCOME MEASURES: We evaluated associations between race/ethnicity and receipt of Covid-19 testing, a positive test result, and 30-day mortality, accounting for a wide range of demographic and clinical risk factors including comorbid conditions, site of care, and urban versus rural residence. RESULTS: Among all individuals in care, 74% were non-Hispanic white (white), 19% non-Hispanic black (black), and 7% Hispanic. Compared with white individuals, black and Hispanic individuals were more likely to be tested for Covid-19 (tests per 1000: white=9.0, [95% CI 8.9 to 9.1]; black=16.4, [16.2 to 16.7]; and Hispanic=12.2, [11.9 to 12.5]). While individuals from minority backgrounds were more likely to test positive (black vs white: OR 1.96, 95% CI 1.81 to 2.12; Hispanic vs white: OR 1.73, 95% CI 1.53 to 1.96), 30-day mortality did not differ by race/ethnicity (black vs white: OR 0.93, 95% CI 0.64 to 1.33; Hispanic vs white: OR 1.07, 95% CI 0.61 to 1.87). CONCLUSIONS: Black and Hispanic individuals are experiencing an excess burden of Covid-19 not entirely explained by underlying medical conditions or where they live or receive care. While there was no observed difference in mortality by race or ethnicity, our findings may underestimate risk in the broader US population as health disparities tend to be reduced in VA.

Covid-19 Testing, Hospital Admission, and Intensive Care Among 2,026,227 United States Veterans Aged 54-75 Years.

IMPORTANCE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes coronavirus disease 2019 (Covid-19), an evolving pandemic. Limited data are available characterizing SARS-Cov-2 infection in the United States. OBJECTIVE: To determine associations between demographic and clinical factors and testing positive for coronavirus 2019 (Covid-19+), and among Covid-19+ subsequent hospitalization and intensive care. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study including all patients tested for Covid-19 between February 8 and March 30, 2020, inclusive. We extracted electronic health record data from the national Veterans Affairs Healthcare System, the largest integrated healthcare system in the United States, on 2,026,227 patients born between 1945 and 1965 and active in care. Exposures: Demographic data, comorbidities, medication history, substance use, vital signs, and laboratory measures. Laboratory tests were analyzed first individually and then grouped into a validated summary measure of physiologic injury (VACS Index). Main Outcomes and Measures: We evaluated which factors were associated with Covid-19+ among all who tested. Among Covid-19+ we identified factors associated with hospitalization or intensive care. We identified independent associations using multivariable and conditional multivariable logistic regression with multiple imputation of missing values. RESULTS: Among Veterans aged 54-75 years, 585/3,789 (15.4%) tested Covid-19+. In adjusted analysis (C-statistic=0.806) black race was associated with Covid-19+ (OR 4.68, 95% CI 3.79-5.78) and the association remained in analyses conditional on site (OR 2.56, 95% CI 1.89-3.46). In adjusted models, laboratory abnormalities (especially fibrosis-4 score [FIB-4] >3.25 OR 8.73, 95% CI 4.11-18.56), and VACS Index (per 5-point increase OR 1.62, 95% CI 1.43-1.84) were strongly associated with hospitalization. Associations were similar for intensive care. Although significant in unadjusted analyses, associations with comorbid conditions and medications were substantially reduced and, in most cases, no longer significant after adjustment. CONCLUSIONS AND RELEVANCE: Black race was strongly associated with Covid-19+, but not with hospitalization or intensive care. Among Covid-19+, risk of hospitalization and intensive care may be better characterized by laboratory measures and vital signs than by comorbid conditions or prior medication exposure.

Alteration of adipose tissue immune cell milieu towards the suppression of inflammation in high fat diet fed mice by flaxseed oil supplementation.

The present study evaluates the effect of flaxseed oil (FXO) supplementation on adipose tissue macrophages (ATM's), E and D series resolvin (Rv) levels and adipose tissue inflammation. Male C57BL/6J mice were divided into five groups (n = 5): lean group (given standard chow diet), HFD group given high fat diet (approx. 18 weeks) till they developed insulin resistance and 4, 8 or 16 mg/kg group (HFD group later orally supplemented with 4, 8 or 16 mg/kg body weight flaxseed oil) for 4 weeks.The present study showed that FXO supplementation led to enhanced DHA, EPA, RvE1-E2, RvD2, RvD5- D6, IL-4, IL-10 and arginase 1 levels in ATMs together with altered immune cell infiltration and reduced NF-κB expression. The FXO supplementation suppresses immune cell infiltration into adipose tissue and alters adipose tissue macrophage phenotype towards the anti-inflammatory state via enhancement of E and D series resolvins, arginase 1 expression and anti-inflammatory cytokines level (IL-4 and IL-10.) leading to amelioration of insulin resistance in flaxseed oil supplemented HFD mice.

Significance of leaf morphoanatomical markers for the authentication of adultered drugs sold in herbal markets of district Lahore, Pakistan.

A number of herbal plants sold in herbal markets of Lahore are under adulteration threat which can pose harmful health effects to end-user. This adulteration problem of medicinal plants can be resolved by the implication of some valuable taxonomic parameter such as leaf epidermal anatomical characteristics. Hence, this research was aimed to provide viable anatomical markers in order to resolve this adulteration issue persisted in some common marketed medicinal plants of district Lahore, that is, Cinnamomum verum Presl., Cinnamomum tamala (Buuch.-Ham.) T.Nees&Eberm., Gymnema sylvestre (Retz.) R.Br.ex Sm., Sphaeranthus indicus Linn., Artemisia maritima Linn., Achillea millifolim L., Adhatoda vasica Nees, Butea monosperma (Lam.) Taub, and Morus nigra L. Overall multiple anatomical variations (epidermal cell shape, their length and width, type of stomata, length and width of guard cells along with presence or absence of trichomes) had been reported in the study that could be worthwhile for the correct identification of medicinal plants. Irregular shapes of epidermal cells were observed in Cinnamomum verum and Achillea millifolium while pentagonal and polygonal cells were found in their adultaerants, that is, Canella winterana and Adhatoda vasica, respectively. Types of stomata were also strikingly varied among genuine plant and its adulterant, for example, anisocytic stomata were observed in Artemisia maritima while in its adulterant (Artemisia absinthium) anomocytic stomata were found. Similarly, paracytic stomata were observed in Butea monosperma, whereas its adulterant plant (Averrhoa carambola) characteristically possessed anisocytic stomata. Hence, anatomical characteristics were proved to be a valuable taxonomic tool in resolving the adulteration issue of medicinal plants.

Microscopic techniques used for the identification of medicinal plants: A case study of Senna.

BACKGROUND: The use of quality control tool for adulteration of Senna (Cassia aungustifolia) a pharmaceutically very important. They were used for multiple health disorders such as constipation, indigestion, epilepsy, asthma, piles, migraine, and heart problems. Two different species of same family or same genus used commercially in Indo-Pak using the same medicine name Senna. One named as Senna (C. aungustifolia) and its adulterant named as Sickle Senna (Cassia obtusifolia). METHODOLOGY: These two plants were analyzed using classical microscopic techniques light microscopy and the modern chemotaxonomic traits scanning electron microscopy, fluorescence studies and phytochemical studies. RESULTS: The C. aungustifolia L. had found to be a perennial herb with trilobed pollen, diacytic, paracytic, and anisocytic stomata having smooth walled epidermal cells, whereas the C. obtusifolia stands out as a perennial shrub with spheroidal and circular pollen and paracytic type of stomata having irregular shaped epidermal cells. The powdered drug of C. aungustifolia is dark grayish green, whereas the powdered drug of C. obtusifolia is light green in color. Investigation and other techniques used in this project provided the basis for the authentication of this species.

Implication of palynological techniques for the authentication of adulterated drugs traded with the same name in different herbal markets of district Lahore, Pakistan.

Adulteration in traded medicinal plants is a significant issue nowadays and use of these adulterated medicinal plants can impose harmful impact to end user. However, this problem can be overcome by ensuring the identification of traded medicinal plants which are used in making different herbal medicines. In this regard, palynological markers are considered to be an important taxonomic tool in the identification of original medicinal plant from its adulterant. Hence this study attempted to provide particular reliable palynological markers for distinguishing selected medicinal plants from their adulterants, that is, Cinnamomum verum versus Canella winterana, Cinnamomum tamala versus Cinnamomum obtusifolium, Gymnema sylvestre versus Gymnema lactiferum, Artemisia maritima versus Artemisia absinthium, Achillea millefolium versus Adhatoda vasaka, Sphaeranthus indicus versus Sphaeranthus africanus, Averrhoa carambola versus Butea monosperma, and Morus nigra versus Morus alba. Results demonstrated great variations in multiple palynological characters between original medicinal plant and its adulterant such as in pollen size, shape, colpi length, exine, intine thickness, and fertility. In equatorial view, circular to spheroidal shape of pollen was found in A. millefolium while oblate shape was observed in A. vasaka. Similarly B. monosperma pollen was 34 µm, whereas pollen of its adulterant A. carambola was 21 µm. Moreover, colpi length of A. maritima was 11.8 µm, whereas 4.5 µm in A. absinthium. Hence it can be concluded that palynological characters are commendably helpful in identification of genuine medicinal plant from its adulterant.

Morpho-palynological assessment of medicinal flora of district Lahore, Pakistan based on LM and SEM.

This study was carried out to identify 20 high valued medicinal plants of District Lahore, Punjab, Pakistan with the help of the palynological studies. The distinguishing characteristics for selected species were found by systematized methods using light microscopy and Scanning Electron Microscopy. In this study, important pollen qualitative and quantitative features of these medicinal species such as polar and equatorial outline and their diameter, P/E ratio, presence or absence of pore, sculpturing of pollen, exine thickness, intine thickness, intercellular distance of exine and intine, presence or absence of spines, length of spines, width of spines, presence or absence of colpi and length of colpi, were compared. Remarkable variations in these pollen characters have been observed. Pollen grains were usually circular-semicircular (Calendula officinalis), spheroidal (Convolvulus arvensis), bilobed and trilobed (Convolvulus arvensis), spiny, (Abutilon indicum), oblate (Terminalia chebula) and elongated (Euphorbia pilulifera). In polar view Conyza bonariensis exhibited the highest pollen size [195.9 (211.6-180.2) µm]. While in equatorial view Calendula officinalis and Euphorbia pilulifera had lowest value [22.5 (20-25) µm] whereas Carissa carandas [165 (140-179) µm] appeared to be the largest. Parthenium hysterophorus showed the highest P/E ratio, that is, 1.28. Colpi were reported in only 7 species. Most of the plants showed 100% fertility but Terminalia chebula showed the least value 35%. In the present, project the diversity in pollen morphology present pollen as a valuable taxonomic tool. It is also concluded that pollen features are helpful at the specific level as well as generic level and can provide us fruitful taxonomic solutions. RESEARCH HIGHLIGHTS: Palynological flora of the medicinal plant species of district Lahore, Pakistan is investigated first time on the basis of LM and SEM and the flora is found very significant for taxonomic investigations.