Extremophiles and Limits of Life in a Cosmic Perspective

Extremophiles are one of the most extreme entity on planet earth which can withstand many harsh conditions considered lethal for other life form of terrestrial life. From an evolutionary prospective, extremophiles are considered to be primitive cells that used to live in the early earths harsh environment living on this planet since billions of years, it can be found in almost in any environmental conditions on our planet. There are many established valuable uses of these extremophiles and particularly their bioactive compounds. The enzymes produced by extremophiles have significant applications in different industries like detergent, food, feed, starch, textile, leather, pulp and paper, and pharmaceuticals This chapter discuss extremophile, their survival mechanism and astrobiology, discussing life in a cosmic prospective

Anti-hyperglycemic activity of Heliotropium strigosum (Boraginaecae) whole plant extract in alloxan-induced diabetic mice

Purpose: To investigate Heliotropium strigosum whole plant extract for its potential to reduce the blood glucose level of alloxan-induced diabetic mice.Methods: Preliminary phytochemical analysis was carried out using standard  procedures. Diabetes was induced in Balb/c mice by injecting alloxan (200 mg/kg i.p.). The crude methanol extract of Heliotropium strigosum (Hs.Cr, 30, 100 and 300 mg/kg doses) was administered daily to alloxan-induced diabetic mice for 15 days and its effect on fasting blood glucose levels, body weight and oral glucose tolerancewas evaluated. Two control groups (non-diabetic control and diabetic control)  received normal saline (0.2 ml). Metformin (500 mg/kg) was used as reference standard.Results: Heliotropium strigosum showed positive for the presence of alkaloids, tannins and flavonoids. The extract (30, 100 and 300 mg/kg) caused significant reduction in the fasting blood glucose level of alloxan-induced diabetic mice on days 5, 10 and 15 compared to diabetic control (p < 0.001). In this regard, the  anti-hyperglycemic effect compared to the reference (metformin). The extract also timedependently decreased the body weight of the treated animals as well as improved tolerance of the oral glucose overload.Conclusion: These results indicate that Heliotropium strigosum possesses  anti-hyperglycemic effect, reduces body weight and enhances the tolerance of  glucose overload in mice. Further studies are therefore required to determine its  feasiilty as an alternate herbal medicine in the management of diabetes in humans.Keywords: Heliotropium strigosum, Anti-hyperglycemic, Alloxan-induced diabetic mice, Blood glucose, Oral glucose tolerance, Body weigh

Prevalence of gastric varices and results of sclerotherapy with N-butyl 2 cyanoacrylate for controlling acute gastric variceal bleeding.

Aim: To study the prevalence, predictors and control of bleeding following N-butyl 2 cyanoacrylate (NBC) sclerotherapy of gastric varix (GV). Methods: We analyzed case records of 1436 patients with portal hypertension, who underwent endoscopy during the past five years for variceal screening or upper gastrointestinal (GI) bleeding. Fifty patients with bleeding GV underwent sclerotherapy with a mean of 2 mL NBC for control of bleeding. Outcome parameters were primary hemostasis (bleeding control within the first 48 h), recurrent bleeding (after 48 h of esophagogastro-duodenoscopy) and in-hospital mortality were analyzed. Results: The prevalence of GV in patients with portal hypertension was 15% (220/1436) and the incidence of bleeding was 22.7% (50/220). Out of the 50 bleeding GV patients, isolated gastric varices (IGV-I) were seen in 22 (44%), gastro-oesophageal varices (GOV) on lesser curvature (GOV-Ⅰ) in 16 (32%), and GOV on greater curvature (GOV-Ⅱ) in 15 (30%). IGV-Ⅰ was seen in 44% (22/50) patients who had bleeding as compared to 23% (39/170) who did not have bleeding (P \u3c 0.003). Primary hemostasis was achieved with NBC in all patients. Re-bleeding occurred in 7 (14%) patients after 48 h of initial sclerotherapy. Secondary hemostasis was achieved with repeat NBC sclerotherapy in 4/7 (57%). Three patients died after repeat sclerotherapy, one during transjugular intrahepatic portosystemic stem shunt (TIPSS), one during surgery and one due to uncontrolled bleeding. Treatment failure-related mortality rate was 6% (3/50). Conclusion: GV can be seen in 15% of patients with f patients with using the tissue adhesive agent butyl cyanoacrylate. Since then several authors have used different sclerosing agents to achieve hemostasis in bleeding gastric varices, including N-butyl-2 cyanoacrylate (histoacryl)[4,8], 2-octyl cyanoacrylate[9], ethanolamine oleate injection[10], gastric variceal banding[11], thrombin[12], sodium tetradecyl sulfate[13]. However, N-butyl 2 cyanoacrylate (NBC) is the only promising agent. Most reports on endoscopic treatment of bleeding gastric varices are small series, case reports, or retrospective reviews[14,15]. Not more than 1000 patients with bleeding GV have been treated with different sclerosing and coagulating agents. Cyanoacrylate injection can achieve primary hemostasis in 70% to 95% of patients with acute GV bleeding, with an early rebleeding rate ranging from 0% to 28% within 48 h[5,7,16]. Different doses of cyanoacrylate are used by different gastroenterologis ts[16,17]. Moreover, dilution ratio of NBC to lipoidal is different[18,19]. However, there is no consensus regarding effective dose and dilution of sclerosing agents. This study was to analyze patients with GV in order to establish predictors of bleeding GV, and the efficacy and safety of NBC in treatment of bleeding GV

Enzyme inhibition and antibacterial potential of 4-Hydroxycoumarin derivatives

The 4-Hydroxycoumarin derivatives are known to show a broad spectrum of pharmacological applications. In this paper we are reporting the synthesis of a new series of 4-Hydroxycoumarin derivatives synthesized through Knovenegal condensation; they were characterized by using UV-Vis, FT-IR, NMR spectroscopies. The synthesized compounds were evaluated for antibacterial activity against Staphylococcus aureus and Salmonella typhimurium strains. The compounds (2), (3) and (8) showed favorable antibacterial activity with zone of inhibitions 26.5± 0.84, 26.0 ± 0.56 and 26.0 ± 0.26 against Staphylococcus aureus (Gram-positive) respectively. However, the compounds (5) and (9) were found more active with 19.5 ± 0.59 and 19.5 ± 0.32 zone of inhibitions against Salmonella typhimurium (Gram-negative). Whereas, in urease inhibition assay, none of the synthesized derivatives showed significant anti-urease activity; although, in carbonic anhydrase-II inhibition assay, the compound (2) and (6) showed enzyme inhibition activity with IC50 values 263±0.3 and 456±0.1, respectively

Do clinical manifestations of Systemic Lupus Erythematosus in Pakistan correlate with rest of Asia?

Objective: Systemic Lupus Erythematosus (SLE) is known to be different among people with different racial, geographical and socio-economic back grounds. Asia has diverse ethnic groups broadly, Orientals in the East and Southeast Asia, Indians in South Asia and Arabs in the Middle East. These regions differ significantly from the Caucasians with reference to SLE. The purpose of this study was, therefore, to delineate the clinical pattern and disease course in Pakistani patients with SLE and compare it with Asian data.Methods: Patients with SLE fulfilling the clinical and laboratory criteria of the American Rheumatism Association admitted at the Aga Khan University Hospital between 1986 and 2001 were studied by means of a retrospective review of their records. The results were compared with various studies in different regions of Asia.Results: Demographically, it was seen that SLE is a disease predominantly of females in their third decade, which is generally consistent with Asian data. There was less cutaneous manifestations, arthritis, serositis, haematological and renal involvement compared to various regions in Asia. The neurological manifestations of SLE, however, place Pakistani patients in the middle of a spectrum between South Asians and other Asian races.CONCLUSION: This study has shown that the clinical characteristics of SLE patients in our country may be different to those of other Asian races. Although our population is similar to South Asians, but clinical manifestations of our SLE patients are considerably different, suggesting some unknown etiology. Further studies are required to confirm the above results and to find statistically sounder associations

The relationship between transformational leadership and job performance: an empirical investigation

The main objective of the present paper is to assess the relationship between transformational leadership and job performance empirically.The study was conducted in the banking sector of Pakistan focusing on six large banks.A total number of 308 responses were collected through survey questionnaire from the bank managers.The data was then coded into SPSS for early stage analysis such as data screening.This was followed through applying SmartPLS to analyze the data and the results have been presented in its standard reporting style.The findings revealed a positive relationship between transformational leadership and job performance in banking sector of Pakistan supporting the hypothesized relationship.Finally, the paper has presented a way forward for future research

Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding. Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124. Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid (5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11 952 (99·5%) received the first dose of the allocated treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18). Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of 5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98). Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a randomised trial

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection