Study program to define a medical and paramedical investigation of man in a closed ecological environment. Volume 2 - Annotated bibliography

Annotated bibliography of literature related to man and animals in closed ecological systems and simulated space environment

Ameliorating potentials of antioxidants on the lead-induced immunotoxicity in male Wistar rats

Lead exposure is a significant environmental and public health concern, known for its detrimental effects on various physiological systems, including the immune system. The study was undertaken to establish the ameliorating action of antioxidants on lead-induced toxicity on immunoglobulins using male Wistar rats as experimental models. One hundred and sixty-two male Wistar rats with weights between 180 and 200 g were obtained from the Experimental Animal Farm of the University of Port Harcourt, Nigeria. The Wistar rats were housed in wooden animal cages in a well-ventilated experimental room. Handling of the animals was in accordance with relevant institutional and ethical guidelines as approved for scientific study. The control group (group 1) was orally given 0.5 ml of distilled water, while the treatment groups (groups 2 to 9) were orally given different substances as follows: 10 mg/kg body weight (BW) of lead only, 200 mg/kg BW of vitamin C only, 1000 iu/kg BW of vitamin E only, 10 mg/kg BW of lead + 200 mg/kg BW of vitamin C, 10 mg/kg BW of lead + 1000 iu/kg BW of vitamin E, 10 mg/kg BW of lead + 40 mg/BW levamisole, 10 mg/kg BW of lead + 200 mg/kg BW of vitamin C + 40 mg/BW levamisole, and 10 mg/kg BW of lead + 1000 iu/kg BW of vitamin E + 40 mg/BW levamisole, respectively, once a day. The experiment was conducted in three phases (phases 1 to 3), which lasted for 7 days (acute phase), 30 days (sub-acute phase), and 60 days (chronic phase). At the end of the experimentation for each phase, five rats were sacrificed, and blood samples were collected from each rat and examined for immunological parameters. The effects of treatment with lead and antioxidants were compared with the control group. There was a significant decrease in the concentrations of the immunoglobulins in the lead group with respect to the control in all the phases. There was also a significant increase in the concentrations of the immunoglobulins in groups 3 and 4 with respect to the control in phases 1 and 2 and a significant increase in the concentrations of the immunoglobulins in groups 5 to 9 with respect to the lead group in all three phases. The antioxidants have, therefore, demonstrated the ability to ameliorate the lead-induced toxicity on the immunoglobulins

Curcuma longa (Turmeric) and Cucumis sativus (Cucumber) Juice Ameliorative Hematological Effects in Lead Induced Toxicity in Male Wistar Rats

Hematological parameters are essential clinical indicators of health status, which are of great research interest. Our study attempts an assessment of the possible ameliorative hematological effects of Turmeric and Cucumber juice in lead induced toxicity using male Wistar rats as models. Experimental animals were acclimatized for 2 weeks and were subsequently randomly distributed into five groups made up of five rats per group. Lead toxicity was induced through a single daily oral administration of 2.25mg/kg body weight of lead in all rat groups except groups1 and 7 for 28 days and were treated as follows: Group 1: Control; animals in this group had free access to tap water and normal rat chow at will. Group 2: Pb only; animals in this group received 2.25mg/kg bw of lead acetate only. Group 3: Pb + TUM; rats in this group got 1ml of Turmeric juice only following induction of lead toxicity. Group 4: Pb + CUC; animals in this group were given 1ml of Cucumber juice only following induction of lead toxicity. Group 5: Pb + TUM + CUC; animals in this group received 1ml of Turmeric and 1ml of Cucumber juice following induction of lead toxicity. Group 6: Pb + bioferon; animals in this group received 0.23ml/kg body weight dose of bioferon following lead induced toxicity. Group 7: Bioferon Only; animals in this group received 0.23ml/kg body weight dose of bioferon only. All administrations were orally carried out once a day in the morning hours (between 8am-9am) using oral cannula. On day 29, experimental animals were anesthetized using diethyl ether and blood samples taken via cardiac puncture for serum erythrocyte parameters (PCV, Hb and RBC) and total WBC and PLT counts determination. Assayed parameters were assessed using a reflotron produced by Boehringer Mannhein. Predictably, administration of 2.25mg/kg bw of lead acetate to group 2 (Pb Only) rats produced a significant reduction (p<0.05) in PCV, Hb, RBC, WBC and PLT counts when compared to group 1 (Control) rats. This is suggestive of a possible deleterious effect of lead acetate at the administered dose. However, administration of 1ml each of turmeric and cucumber juice respectively significantly increased (p<0.05) the above parameters amongst groups 3 (Pb + TUM) and 4 (Pb + CUC) rats when compared to group 2 (Pb Only) rats with turmeric showing a better effect. Significantly higher (p<0.05) values of PCV, Hb, RBC, WBC, and platelet counts were observed amongst group 5 (Pb + TURM + CUC) rats co-administered 1ml each of both turmeric and cucumber juice, compared togroups1 (Control), 2 (PbOnly), 3 (Pb + TUM) and 4 (Pb + CUC) rats. Indicating a possible greater hematopoietic effect of the combined administration of both juices compared to single administration of either juice. Our findings suggest a possible synergistic effects of the juices on haematological indices when combined following lead administration in experimental rats

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations: an overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO)

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included

Reinforcement Learning versus Swarm Intelligence for Autonomous Multi-HAPS Coordination

This work analyses the performance of Reinforcement Learning (RL) versus Swarm Intelligence (SI) for coordinating multiple unmanned High Altitude Platform Stations (HAPS) for communications area coverage. It builds upon previous work which looked at various elements of both algorithms. The main aim of this paper is to address the continuous state space challenge within this work by using partitioning to manage the high dimensionality problem. This enabled comparing the performance of the classical cases of both RL and SI establishing a baseline for future comparisons of improved versions. From previous work, SI was observed to perform better across various key performance indicators. However, after tuning parameters and empirically choosing suitable partitioning ratio for the RL state space, it was observed that the SI algorithm still maintained superior coordination capability by achieving higher mean overall user coverage (about 20% better than the RL algorithm), in addition to faster convergence rates. Though the RL technique showed better average peak user coverage, the unpredictable coverage dips was a key weakness, making SI a more suitable algorithm within the context of this work

An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes

Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species in vivo screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.We are grateful to F.B. Gertler (Massachusetts Institute of Technology) and S. Gupton (University of North Carolina) for the generous gift of the VAMP7-phlorin construct and the staffs of the Hartwell Center for Bioinformatics and Biotechnology, the Small Animal Imaging Center, the Animal Resources Center, the Cell and Tissue Imaging Center, and the Flow Cytometry and Cell Sorting Shared Resource at St. Jude Children's Research Hospital for technical assistance. This work was supported by grants from the US National Institutes of Health (R01CA129541, P01CA96832 and P30CA021765, R.J.G.), by the Collaborative Ependymoma Research Network (CERN) and by the American Lebanese Syrian Associated Charities (ALSAC)

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort

Objectives:We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies.Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries.Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT(> MIC) (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving beta-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of >= 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025].Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

Scaling the state: Egypt in the third millennium BC

Discussions of the early Egyptian state suffer from a weak consideration of scale. Egyptian archaeologists derive their arguments primarily from evidence of court cemeteries, elite tombs, and monuments of royal display. The material informs the analysis of kingship, early writing, and administration but it remains obscure how the core of the early Pharaonic state was embedded in the territory it claimed to administer. This paper suggests that the relationship between centre and hinterland is key for scaling the Egyptian state of the Old Kingdom (ca. 2,700-2,200 BC). Initially, central administration imagines Egypt using models at variance with provincial practice. The end of the Old Kingdom demarcates not the collapse, but the beginning of a large-scale state characterized by the coalescence of central and local models