Contemplation Impact of Pulp Seeds Cucurbita Pepo L. and its Paste on Oxidative Stress in Rats

Cucurbita Pepo L. seeds and seeds paste which are rich sources of phytochemicals and act as a rich source of antioxidants. The most important phytochemicals present in the cucurbits are cucurbitacin’s, saponins, carotenoids, phytosterols, and polyphenols. These bioactive phyto-constituents are responsible for the pharmacological effects including antioxidant effect. Aim of this study was to investigate the effect of Cucurbita Pepo L. seeds and seeds paste on rats suffering from oxidative stress. Thirty-six male albino rats were used in the experiment (Sprague-Dawley strain). The animals randomly divided 6 rats each group according to the following the first Group: Rats were fed basal diet and set as negative control. The other rats (n = 30) were fed on basal diet containing monosodium glutamate (120 mg/kg) for induce stress condition. After that, rats further divided into 5 groups (n = 6) each for six weeks as follows: -2nd Group: Rats were fed on basal diet containing monosodium glutamate and set as positive control. 3rd Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds 5%. 4th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds 10%. 5th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds paste 5%. 6th Group: Rats were fed on diet containing monosodium glutamate with addition of Cucurbita Pepo L. seeds paste 10%. The experimental period was six weeks; Blood samples were collected. At the end of the experiment, the results showed that using seeds 5% & 10% and seeds paste 5% & 10% in feeding the stressed rats increased (BWG%, FI, FER, Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx)) with highest results in group fed on 10% seeds paste and decreased (Urea, Creatinine, ALT, AST, IL-6 and INF-gamma) with lowest results in group fed on 10% Cucurbita Pepo L. seeds paste

Increase in Caesarean Deliveries after the Australian Private Health Insurance Incentive Policy Reforms

AbstractBackground: The Australian Private Health Insurance Incentive (PHII) policy reforms implemented in 1997–2000 increased PHI membership in Australia by 50%. Given the higher rate of obstetric interventions in privately insured patients, the reforms may have led to an increase in surgical deliveries and deliveries with longer hospital stays. We aimed to investigate the effect of the PHII policy introduction on birth characteristics in Western Australia (WA).Methods and Findings: All 230,276 birth admissions from January 1995 to March 2004 were identified from administrative birth and hospital data-systems held by the WA Department of Health. Average quarterly birth rates after the PHII introduction were estimated and compared with expected rates had the reforms not occurred. Rate and percentage differences (including 95% confidence intervals) were estimated separately for public and private patients, by mode of delivery, and by length of stay in hospital following birth. The PHII policy introduction was associated with a 20% (221.4 to219.3) decrease in public birth rates, a 51% (45.1 to 56.4) increase in private birth rates, a 5% (25.3 to 25.1) and 8% (28.9 to 27.9) decrease in unassisted and assisted vaginal deliveries respectively, a 5% (25.3 to 25.1) increase in caesarean sections with labour and 10% (8.0 to 11.7) increase in caesarean sections without labour. Similarly, birth rates where the infant stayed 0–3 days in hospital following birth decreased by 20% (221.5 to 218.5), but rates of births with .3 days inhospital increased by 15% (12.2 to 17.1).Conclusions: Following the PHII policy implementation in Australia, births in privately insured patients, caesarean deliveries and births with longer infant hospital stays increased. The reforms may not have been beneficial for quality obstetric care in Australia or the burden of Australian hospitals

The Three Hundred Project: the gizmo-simba run

We introduce gizmo-simba, a new suite of galaxy cluster simulations within The Three Hundred project. The Three Hundred consists of zoom re-simulations of 324 clusters with M 200≳ 1014.8, M ⊙ drawn from the MultiDark-Planck N-body simulation, run using several hydrodynamic and semi-analytical codes. The gizmo-simba suite adds a state-of-the-art galaxy formation model based on the highly successful Simba simulation, mildly re-calibrated to match z = 0 cluster stellar properties. Comparing to The Three Hundred zooms run with gadget-x, we find intrinsic differences in the evolution of the stellar and gas mass fractions, BCG ages, and galaxy colour-magnitude diagrams, with gizmo-simba generally providing a good match to available data at z ≈ 0. gizmo-simba's unique black hole growth and feedback model yields agreement with the observed BH scaling relations at the intermediate-mass range and predicts a slightly different slope at high masses where few observations currently lie. Gizmo-Simba provides a new and novel platform to elucidate the co-evolution of galaxies, gas, and black holes within the densest cosmic environments

Cancer incidence and mortality trends in Australian adolescents and young adults, 1982-2007

Background: Increasing incidence and lack of survival improvement in adolescents and young adults (AYAs) with cancer have led to increased awareness of the cancer burden in this population. The objective of this study was to describe overall and type-specific cancer incidence and mortality trends among AYAs in Western Australia from 1982-2007.Methods: Age-adjusted incidence and mortality rates were calculated for all malignancies combined and for each of the most common diagnostic groups, using five-year age-specific rates. Joinpoint regression analysis was used to derive annual percentage changes (APC) for incidence and mortality rates.Results: The annual incidence rate for all cancers combined increased in males from 1982 until 2000 (APC = 1.5%, 95%CI: 0.9%; 2.1%) and then plateaued, whilst rates for females remained stable across the study period (APC = -0.1%; 95%CI: -0.2%; 0.4%) across the study period. For males, significant incidence rate increases were observed for germ cell tumors, lymphoblastic leukemia and thyroid cancer. In females, the incidence of Hodgkin's lymphoma, colorectal and breast cancers increased. Significant incidence rate reductions were noted for cervical, central nervous system and lung cancers. Mortality rates for all cancers combined decreased from 1982 to 2005 for both males (APC = -2.6%, 95%CI:-3.3%;-2.0%) and females (APC = -4.6%, 95%CI:-5.1%;-4.1%). With the exception of bone sarcoma and lung cancer in females, mortality rates for specific cancer types decreased significantly for both sexes during the study period.Conclusions: Incidence of certain AYA cancers increased, whilst it decreased for others. Mortality rates decreased for most cancers, with the largest improvement observed for breast carcinomas. Further research is needed to identify the reasons for the increasing incidence of certain cancers. © 2012 Haggar et al.; licensee BioMed Central Ltd

CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with Bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973]

BACKGROUND: Chagas' disease is the major cause of disability secondary to tropical diseases in young adults from Latin America, and around 20 million people are currently infected by T. cruzi. Heart failure due to Chagas cardiomyopathy is the main clinical presenation in Colombia. Heart failure due to Chagas' disease may respond to digoxin, diuretics and vasodilator therapy. Beta-adrenoreceptor antagonism seems to protect against the increased risk of cardiac arrhythmia and sudden death due to chronic sympathetic stimulation. The aim of this study is to evaluate the effects of the selective beta-adrenergic receptor blocker Bisoprolol on cardiovascular mortality, hospital readmission due to progressive heart failure and functional status in patients with heart failure secondary to Chagas' cardiomyopathy. METHODS/DESIGN: A cohort of 500 T. cruzi seropositive patients (250 per arm) will be selected from several institutions in Colombia. During the pretreatment period an initial evaluation visit will be scheduled in which participants will sign consent forms and baseline measurements and tests will be conducted including blood pressure measurements, twelve-lead ECG and left ventricular ejection fraction assessment by 2D echocardiography. Quality of life questionnaire will be performed two weeks apart during baseline examination using the "Minnesota living with heart failure" questionnaire. A minimum of two 6 minutes corridor walk test once a week over a two-week period will be performed to measure functional class. During the treatment period patients will be randomly assigned to receive Bisoprolol or placebo, initially taking a total daily dose of 2.5 mgrs qd. The dose will be increased every two weeks to 5, 7.5 and 10 mgrs qd (maximum maintenance dose). Follow-up assessment will include clinical check-up, and blood collection for future measurements of inflammatory reactants and markers. Quality of life measurements will be obtained at six months. This study will allow us to explore the effect of beta-blockers in chagas' cardiomyopathy

Cancer Survival and Excess Mortality Estimates among Adolescents and Young Adults in Western Australia, 1982-2004: A Population-Based Study

Background: Data are limited on cancer outcomes in adolescents and young adults. Methods: Based on data from the Western Australian Data Linkage System, this study modelled survival and excess mortality in all adolescents and young adults aged 15-39 years in Western Australia who had a diagnosis of cancer in the period 1982-2004. Relative survival and excess all-cause mortality for all cancers combined and for principal tumour subgroups were estimated, using the Ederer II method and generalised linear Poisson modelling, respectively. Results: A cancer diagnosis in adolescents and young adults conferred substantial survival decrement. However, overall outcomes improved over calendar period (excess mortality hazard ratio [HR], latest versus earliest diagnostic period: 0.52, trend <0.0001). Case fatality varied according to age group (HR, oldest versus youngest: 1.38, trend <0.0001), sex (HR, female versus male: 0.66, 95% confidence interval [CI] 0.62-0.71), ethnicity (HR, Aboriginal versus others: 1.47, CI 1.23-1.76), geographical area (HR, rural/remote versus urban: 1.13, CI 1.04-1.23) and residential socioeconomic status (HR, lowest versus highest quartile: 1.14, trend <0.05). Tumour subgroups differed substantially in frequency according to age group and sex, and were critical outcome determinants. Conclusions: Marked progressive calendar-time improvement in overall outcomes was evident. Further research is required to disentangle the contributions of tumour biology and health service factors to outcome disparities between ethno-demographic, geographic and socioeconomic subgroups of adolescents and young adults with cancer. © 2013 Haggar et al

Higher dose corticosteroids in patients admitted to hospital with COVID-19 who are hypoxic but not requiring ventilatory support (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: Low-dose corticosteroids have been shown to reduce mortality for patients with COVID-19 requiring oxygen or ventilatory support (non-invasive mechanical ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation). We evaluated the use of a higher dose of corticosteroids in this patient group. METHODS: This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing multiple possible treatments in patients hospitalised for COVID-19. Eligible and consenting adult patients with clinical evidence of hypoxia (ie, receiving oxygen or with oxygen saturation <92% on room air) were randomly allocated (1:1) to either usual care with higher dose corticosteroids (dexamethasone 20 mg once daily for 5 days followed by 10 mg dexamethasone once daily for 5 days or until discharge if sooner) or usual standard of care alone (which included dexamethasone 6 mg once daily for 10 days or until discharge if sooner). The primary outcome was 28-day mortality among all randomised participants. On May 11, 2022, the independent data monitoring committee recommended stopping recruitment of patients receiving no oxygen or simple oxygen only due to safety concerns. We report the results for these participants only. Recruitment of patients receiving ventilatory support is ongoing. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between May 25, 2021, and May 13, 2022, 1272 patients with COVID-19 and hypoxia receiving no oxygen (eight [1%]) or simple oxygen only (1264 [99%]) were randomly allocated to receive usual care plus higher dose corticosteroids (659 patients) versus usual care alone (613 patients, of whom 87% received low-dose corticosteroids during the follow-up period). Of those randomly assigned, 745 (59%) were in Asia, 512 (40%) in the UK, and 15 (1%) in Africa. 248 (19%) had diabetes and 769 (60%) were male. Overall, 123 (19%) of 659 patients allocated to higher dose corticosteroids versus 75 (12%) of 613 patients allocated to usual care died within 28 days (rate ratio 1·59 [95% CI 1·20–2·10]; p=0·0012). There was also an excess of pneumonia reported to be due to non-COVID infection (64 cases [10%] vs 37 cases [6%]; absolute difference 3·7% [95% CI 0·7–6·6]) and an increase in hyperglycaemia requiring increased insulin dose (142 [22%] vs 87 [14%]; absolute difference 7·4% [95% CI 3·2–11·5]). INTERPRETATION: In patients hospitalised for COVID-19 with clinical hypoxia who required either no oxygen or simple oxygen only, higher dose corticosteroids significantly increased the risk of death compared with usual care, which included low-dose corticosteroids. The RECOVERY trial continues to assess the effects of higher dose corticosteroids in patients hospitalised with COVID-19 who require non-invasive ventilation, invasive mechanical ventilation, or extracorporeal membrane oxygenation. FUNDING: UK Research and Innovation (Medical Research Council), National Institute of Health and Care Research, and Wellcome Trust

Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods: RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69–0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86–1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (<1%) participants were believed by the local investigator to be related to treatment with casirivimab and imdevimab. Interpretation: In patients admitted to hospital with COVID-19, the monoclonal antibody combination of casirivimab and imdevimab reduced 28-day mortality in patients who were seronegative (and therefore had not mounted their own humoral immune response) at baseline but not in those who were seropositive at baseline. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Baricitinib in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial and updated meta-analysis

Background: We aimed to evaluate the use of baricitinib, a Janus kinase (JAK) 1–2 inhibitor, for the treatment of patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised with COVID-19 in the UK. Eligible and consenting patients were randomly allocated (1:1) to either usual standard of care alone (usual care group) or usual care plus baricitinib 4 mg once daily by mouth for 10 days or until discharge if sooner (baricitinib group). The primary outcome was 28-day mortality assessed in the intention-to-treat population. A meta-analysis was done, which included the results from the RECOVERY trial and all previous randomised controlled trials of baricitinib or other JAK inhibitor in patients hospitalised with COVID-19. The RECOVERY trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936) and is ongoing. Findings: Between Feb 2 and Dec 29, 2021, from 10 852 enrolled, 8156 patients were randomly allocated to receive usual care plus baricitinib versus usual care alone. At randomisation, 95% of patients were receiving corticosteroids and 23% were receiving tocilizumab (with planned use within the next 24 h recorded for a further 9%). Overall, 514 (12%) of 4148 patients allocated to baricitinib versus 546 (14%) of 4008 patients allocated to usual care died within 28 days (age-adjusted rate ratio 0·87; 95% CI 0·77–0·99; p=0·028). This 13% proportional reduction in mortality was somewhat smaller than that seen in a meta-analysis of eight previous trials of a JAK inhibitor (involving 3732 patients and 425 deaths), in which allocation to a JAK inhibitor was associated with a 43% proportional reduction in mortality (rate ratio 0·57; 95% CI 0·45–0·72). Including the results from RECOVERY in an updated meta-analysis of all nine completed trials (involving 11 888 randomly assigned patients and 1485 deaths) allocation to baricitinib or another JAK inhibitor was associated with a 20% proportional reduction in mortality (rate ratio 0·80; 95% CI 0·72–0·89; p<0·0001). In RECOVERY, there was no significant excess in death or infection due to non-COVID-19 causes and no significant excess of thrombosis, or other safety outcomes. Interpretation: In patients hospitalised with COVID-19, baricitinib significantly reduced the risk of death but the size of benefit was somewhat smaller than that suggested by previous trials. The total randomised evidence to date suggests that JAK inhibitors (chiefly baricitinib) reduce mortality in patients hospitalised for COVID-19 by about one-fifth. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

BACKGROUND: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. METHODS: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). FINDINGS: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). INTERPRETATION: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids