DNA Damage Estimation after Chronic and Combined Exposure to Endocrine Disruptors: An In Vivo Real-Life Risk Simulation Approach.

Exposure to chemical substances has always been a matter of concern for the scientific community. During the last few years, researchers have been focusing on studying the effects resulting from combined exposure to different substances. In this study, we aimed to determine the DNA damage caused after chronic and combined exposure to substances characterized as endocrine disruptors using comet and micronuclei assays, specifically glyphosate (pure and commercial form), bisphenol A, parabens (methyl-, propyl- and butylparaben), triclosan and bis (2-ethylhexyl) phthalate. The highest mean tail intensity was observed in the group exposed to a high-dose (10 × ADI) mixture of substances (Group 3), with a mean value of 11.97 (11.26-13.90), while statistically significant differences were noticed between the groups exposed to low-dose (1 × ADI) (Group 2) and high-dose (10 × ADI) (Group 3) mixtures of substances (p = 0.003), and between Group 3 and both groups exposed to high doses (10 × ADI) of the pure and commercial forms of glyphosate (Groups 4 (p = 0.014) and 5 (p = 0.007)). The micronuclei assay results were moderately correlated with the exposure period. Group 5 was the most impacted exposure group at all sampling times, with mean MN counts ranging between 28.75 ± 1.71 and 60.75 ± 1.71, followed by Group 3 (18.25 ± 1.50-45.75 ± 1.71), showing that commercial forms of glyphosate additives as well as mixtures of endocrine disruptors can enhance MN formation. All exposure groups showed statistically significant differences in micronuclei counts with an increasing time trend.

Role of Inherited Thrombophilia Risk Factors in Patients with CKD-5 Receiving Haemodialysis.

BACKGROUND: The inherited thrombophilic mutations of the factor V gene (FVG1691A Leiden-FVL), prothrombin gene (PTG20210A), and the methylenetetrahydrofolate reductase gene C677T (MTHFR C677T) are risk factors for thromboembolic events and are related to the pathogenesis of vascular diseases. OBJECTIVES: The main objective of this study was to explore the role of these factors in the pathogenesis of chronic kidney disease (CKD) and survival of patients with CKD-5 receiving haemodialysis. METHODS: A cohort of 395 patients with CKD-5 on haemodialysis, from 6 dialysis units in Crete, Greece were recruited based on their medical records and were followed for 5 years. We collected data on CKD-5 aetiology, thrombophilic gene expression, vascular access thrombosis, time of death, and causes of death. RESULTS: The mutated genes just as prevalent in patients with CKD-5 as they were in a control group with no renal disease (p > 0.05). FVL heterozygosity was significantly more prevalent (11.4 vs. 5.7%; p = 0.036) in patients presented with CKD of unknown aetiology, compared to CKD secondary to known aetiologies. The survival of patients with CKD-5 receiving haemodialysis was not affected by the presence of any thrombophilic mutation. This held true for the whole cohort and for the cohort that included only lethal vascular events. Most patients with MTHFR C677T heterozygosity, and all patients with MTHFR C677T homozygosity, died from vascular events during the follow-up period. CONCLUSION: The FVL mutation may act as a risk factor for CKD. This study increases our understanding of molecular mechanisms in the pathogenesis of CKD of unknown aetiology. Τhe presence of thrombophilic mutations did not affect the overall survival of patients with CKD-5. This finding probably reflects the effect of medical care on patient outcomes.

Investigating exposure to endocrine disruptors via hair analysis of pregnant women.

The aim of this study was the monitoring of the levels of parabens (PBs) and triclosan (TCS) in head hair samples of women collected during the first months of their pregnancy. Personal details concerning somatometric and demographic characteristics, dietary habits, use of personal care products and the medical and obstetrical history of the pregnant women as well as infants' somatometric characteristics and health condition were recorded through relevant questionnaires. Ninety five hair samples were collected, extracted by solid-liquid extraction and analysed using a liquid chromatography-mass spectrometry system (LC-MS). Analysis revealed high percentage of positive samples for all tested compounds (90-100% except from BePB (15.8%)). The mean concentration levels were 4501.2 pg/mg (17.6-27,437.0 pg/mg) for MePB; 510.1 pg/mg (11.0-4224.5 pg/mg) for EtPB; 22.9 pg/mg (2.1-66.6 pg/mg) for BePB; 237.1 pg/mg (1.8-2513.7 pg/mg) for BuPB and 245.0 pg/mg (8.8-8070.2 pg/mg) for TCS. Statistical analysis of both analytical results and questionnaires' data showed that the frequent use of personal care and hygiene products, such as makeup, hairspray and sunscreens, is correlated with higher levels of PBs in hair of the pregnant women. Additionally, positive correlation was observed between the BePB levels in hair and the infants' height. Finally, no other correlation was observed between endocrine disruptors' levels in maternal hair and infants' somatometric characteristics or health condition. Our study is the first one that determined PBs and TCS levels in hair samples, simultaneously. At the same time, correlation of the detected levels with the use of personal care products was accomplished, leading to significant association of BePB levels in hair of pregnant women with infants' height.

Nonlinear responses to waterborne cadmium exposure in zebrafish. An in vivo study.

Cadmium (Cd) has proved to be associated with numerous toxic effects in aquatic organisms via waterborne exposure. With a view to investigate Cd toxicity along a broad spectrum of exposures reaching from environmental to toxic, we employed adult zebrafish (Danio rerio) for an in vivo study. A number of 10 fish per tank were placed in 40L tanks and were exposed for 30 days to 0.0, 5.0, 25, 50, 75, 100 and 1000µgCd per liter. There were 2 tanks for each Cd exposure (duplicate experiment). Mortality was recorded daily, dead fish were collected and tissue samples were obtained for histologic observation, whereas remaining tissues were stored for Cd burden determination. Surviving fish were collected at the end of the experiment. Median overall survival (OS) in days was found to be 9.0, 11.0, 8.0 and 7.0 for 25µg/L, 50µg/L, 75µg/L and 100µg/L respectively, with all of them showing mortality greater than 50%. Remarkably, fish exposed to the highest Cd concentration (1000µg/L) survived the longest exhibiting a mean OS of 29.2 days. Cd determination in fish tissue was conducted with an in house ICP-MS method and levels ranged from 3.1 to 29.1ng/mg. Log Cd tissue levels were significantly correlated with the log Cd exposure levels (r = 0.535, p < 0.001). The highest Cd burden was determined for fish exposed to 1000µgCd /L (mean = 12.2ng/mg). Histopathology supported these results. Our findings disclose a deviation in toxic responses through the range of Cd concentrations, leading to nonlinear responses. These differentiated responses, could be linked to hormesis phenomena.

Long lasting effects of chronic heavy cannabis abuse.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the extent of short-term memory impairment and schizophrenia-like symptoms in heavy and systematic cannabis users and the association between the severity of abuse and the longevity of its persistent symptoms after refraining from such use. METHODS: A complete psychiatric examination and a psychometric evaluation were performed in 48 solely cannabis users. Additionally, head hair samples were analyzed and the detected cannabinoids levels were correlated with the psychometric findings. RESULTS: A total of 33.3% (n = 16) of the total examined cannabis users were currently imprisoned. The years of abuse ranged from 1 to 35 years and the median daily dose was 5.84.4 gr and 4.84.0 gr for prisoners (n = 16) and non prisoners (n = 32), respectively. A total of 39.6% of the users experienced hallucinations (mostly auditory), 54.2% experienced delusions (mostly ideas of reference and persecution), 85.4% had organic brain dysfunction in a test addressing visual-motor functioning and visual perception skills, and all users (100%) were found to have organic brain dysfunction in a test of visual memory immediate recall. The cannabinoid metabolite levels in the hair samples were consistent with the reported history of substance abuse and total grams of consumption for the participants below 35 years old (p < .001). Statistically elevated cannabinoids levels were observed in users with auditory hallucinations compared to users without any hallucinations (p = .019). CONCLUSIONS: The existence of hallucinations, delusions, and organic brain dysfunction in heavy cannabis users seems to be associated with cannabinoid levels in hair. The continuation of persistent symptoms 3 months after the discontinuation of cannabis abuse, was a remarkable finding. SCIENTIFIC SIGNIFICANCE: We provide evidence that chronic and heavy cannabis abuse results in long-lasting brain dysfunction in all users and in long-lasting schizophrenia-like psychotic symptoms in more than half of all users. These findings suggest a reevaluation of the current classification of cannabis as a "soft narcotic" which erroneously, therefore, is typically considered harmless. (Am J Addict 2017;26:335-342).

Centhaquin improves survival in a swine model of hemorrhagic shock.

BACKGROUND: Hemorrhage is a frequent event in hospital and prehospital settings. The aim of the present study was to investigate whether centhaquin improves 24-h survival and reduces the total volume of required fluids in an established model of swine hemorrhagic shock. MATERIAL AND METHODS: Twenty-five pigs were instrumented and subjected to hemorrhagic shock. The animals were randomly allocated in two experimental groups, the control (vehicle) (n = 10) and the centhaquin groups (0.015 mg/kg, n = 10); all animals received lactated Ringer solution in the resuscitation phase until their mean arterial pressure reached 90% of the baseline. A sham group (n = 5) was added a posteriori to mimic the hemodynamic profile of the centhaquin group. RESULTS: A statistically significant difference was observed in the time required for the three groups to reach their target mean aortic pressure, 36.88 ± 3.26 min for the control group versus 9.40 ± 1.01 min for the sham group and 7.10 ± 0.97 min for the centhaquin group (P < 0.001). The total amount of fluids in the control and the sham groups was significantly higher when compared with that of the centhaquin-treated animals (P < 0.001). All 10 animals in the centhaquin group survived for 24 h, whereas only three animals survived in the control group and one animal in the sham group (P = 0.002). CONCLUSIONS: Centhaquin 0.015 mg/kg administered in the fluid resuscitation phase resulted in lower volume of fluids and better survival compared with control and sham-operated animals.

High density of tryptase-positive mast cells in patients with multiple myeloma: correlation with parameters of disease activity.

Multiple myeloma (MM) is a plasma cell neoplasm characterized by bone marrow infiltration from malignant plasma cells. Mast cells play an important role in inflammation and angiogenesis in malignant diseases. The aim of the study was to evaluate the mast cell density in bone marrow of untreated MM patients with markers of disease activity such as serum interleukin-6 (IL-6), B2M, and C-reactive protein (CRP), the grade of bone marrow infiltration, and the levels of produced paraprotein. We studied 86 newly diagnosed MM patients (46 males, 40 females, mean age 59 ± 13.7 years). Thirty of them reached plateau phase after chemotherapy and 20 healthy volunteers. According to the criteria of International Staging System (ISS) staging system, 23 patients had stage I, 30 had stage II, and 33 had stage III. The serum concentrations of CRP, B2M, and IL-6, and the mast cell density (MCD) values were significantly higher in MM patients' group (1.6 ± 1.8, 4.3 ± 2.9, 7.1 ± 5.1, and 9 ± 4.8), in comparison with those found in control group (0.4 ± 0.1, 1.5 ± 0.6, 1.1 ± 0.5, and 1.9 ± 0.7; p < 0.001 in all the cases). Significant differences were found between the grade of infiltration in bone marrow, and the paraprotein values in patients' serum before and after chemotherapy. Furthermore, there was a significant correlation between the MCD values and the prognostic markers CRP (r = 0.452, p < 0.0001), IL-6 (r = 0.475, p < 0.0001), bone marrow infiltration (r = 0.333, p < 0.0002), and serum paraprotein levels(r = 0.221, p < 0.04). High MCD values strengthen the hypothesis that mast cells participate in the pathogenesis of disease progression and may be used as an indicator of the disease activity.

Biomonitoring of dialkylphosphate metabolites (DAPs) in urine and hair samples of sprayers and rural residents of Crete, Greece.

PURPOSE: The aim of this study was to evaluate the exposure of rural residents (control group) and occupational exposed population group of sprayers to organophosphorus pesticides (OPs) by measuring their non-specific dialkylphosphate metabolites (DAPs) in hair and in urine samples. All subjects (n=120) were residents of the municipality of Ierapetra, an area of intensive cultivation in Crete, Greece. METHODS: The determined OPs metabolites were DMP, DEP, DETP and DEDTP. Two different approaches were used for the analysis of the collected samples; solid-liquid extraction with sonication for hair and liquid-liquid extraction for urine. Gas chromatography-mass spectrometry (GC-MS) analysis was performed after derivatization of the isolated analytes. RESULTS AND DISCUSSION: The detection rates of DMP, DEP and DETP for both control and sprayers groups were high in both matrices, ranging from 91% to 100%. DEDTP was detected only in 9% of sprayers hair samples, while its detection rates in urine samples ranged from 83% to 90% for both population groups. Data analysis revealed significantly higher sumDAPs levels in urine of sprayers than in the urine of control group (p<0.001) and this is justified since sampling occurred during spraying periods. SumDAPs levels in hair samples of the sprayers were also significantly higher than in the hair of control group (p<0.001), confirming the long-term exposure to OPs. SumDAPs found levels in urine and hair samples of subjects were significantly correlated (Spearman׳s rho=0.728, p<0.001). Our study confirmed the elevated levels of DAPs in hair and urine samples in occupationally exposed group of sprayers in comparison to control group, even detected levels were similar in logarithmic scale.

Acute coagulopathy in children with multiple trauma: a retrospective study.

BACKGROUND: Acute coagulopathy associated with trauma has been recognized for decades and is a constituent of the "triad of death" together with hypothermia and acidosis. STUDY OBJECTIVE: The aim of this study was to determine to what extent coagulopathy is already established upon emergency department (ED) admission and the association with the severity of injury, impaired outcome, and mortality. METHODS: Ninety-one injured children were admitted to the ED in our hospital. Pediatric Trauma Score (PTS), Injury Severity Score (ISS), and Glasgow Coma Scale (GCS) score were used to estimate injury severity, and organ function was assessed by the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Coagulopathy upon pediatric intensive care unit admission was present in 33 children (39.3%): 21 males and 12 females. PTS ranged from 1 to 12 (mean 8.2) in 51 children without coagulopathy and from -1 to +11 (mean 6.8) in 33 children with coagulopathy (p = 0.087). ISS and GCS ranged from 4 to 57 (mean 28) and from 3 to 11 (mean 7.3), respectively, in the coagulopathy group, whereas in the group without coagulopathy, ISS score ranged from 4 to 41 (mean 20.5; p = 0.08) and GCS from 8 to 15 (mean 12.8; p = 0.01). SOFA ranged from 0 to 10 (mean 3.4) in children without coagulopathy and from 0 to 15 (mean 5.4) in the coagulopathy group (p = 0.002). Among 33 children with coagulopathy, 7 did not survive (21%), all with parenchymal brain damage, whereas all trauma patients without coagulopathy survived (p < 0.001). CONCLUSION: Acute coagulopathy is present on admission to the ED and is associated with injury severity and significantly higher mortality.

Evaluation of various blood biomarkers associated with the outcomes of patients with COVID­19 treated in intensive care units.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) represented a global public health crisis and the most significant pandemic in modern times. Transmission characteristics, and the lack of effective antiviral treatment protocol and protective vaccines, pushed healthcare systems, particularly intensive care units (ICUs), to their limits and led to extreme quarantine measures to control the pandemic. It was evident from an early stage that patient stratification approaches needed to be developed to better predict disease progression. In the present study, the predictive value of clinical and blood biomarkers for the outcomes of patients with COVID-19 hospitalized in the ICU were investigated, taking age and sex into consideration. The present study analyzed blood samples from 3,050 patients with COVID-19 hospitalized in the ICU. The analysis revealed that the levels of procalcitonin, N-terminal pro-B-type natriuretic peptide, D-dimer, ferritin, liver enzymes, C-reactive protein and lactate dehydrogenase were increased and were associated with disease progression, resulting in a prolonged hospitalization period and severe COVID-19 related complications. Additionally, significant age and sex disparities among these biomarkers were documented and discussed in specific cases. On the whole, the results of the present study suggest a potential association of the demographic characteristics and blood biomarkers with prolonged hospitalization in the ICU and the mortality of patients with COVID-19.

Serum levels of angiopoietin-2 are associated with the growth of multiple myeloma.

Angiopoietins and their receptor, Tie-2, have crucial role in angiogenesis. We measured serum levels of angiopoietin-2 (Ang-2), soluble Tie-2, and factors of burden and prognosis in myeloma (LDH, CRP, beta-2 microglobulin, and interleukin-6) in 55 newly diagnosed patients, with 30 of them in plateau phase, in order to note correlations among them. Levels of Ang-2 were higher in patients in advanced stage of disease, decreased in plateau phase, and correlated with all other factors. Circulating Ang-2 in myeloma patients significantly correlated to factors of disease burden and prognosis, and therefore measuring its levels may be important for the valuation of the disease.

Stress and Prevalence of Musculoskeletal Disorders Among the Nursing Personnel of a Tertiary Hospital Unit in Greece: A Cross-Sectional Study.

BACKGROUND: Work-related musculoskeletal injuries and disorders (WMSD) are a significant cause of morbidity in the health care sector. Healthcare professionals are routinely exposed to various physical and psychosocial factors that increase the risk of developing a WMSD. Nurses are more susceptible to the manifestation of such disorders. METHODS: A cross-sectional study was conducted during the second semester of 2020. The Nordic Questionnaire (NMQ) was used to investigate the prevalence of musculoskeletal symptoms, the Short Anxiety Screening Test (SAST) for stress detection, and a data collection sheet was developed for the registration of clinical, demographic, and anthropometric characteristics of the nursing personnel of the tertiary hospital unit of Heraklion, Crete, Greece. RESULTS: A percentage of 82% of nurses had developed at least one musculoskeletal symptom in the last 12 months. The most common anatomical areas at which symptoms were present the last 12 months were the neck (53.9%), shoulders (50.8%), and the lower back (49.5%). The same areas were also the reported anatomical regions, most affected by musculoskeletal symptoms when stress levels were high. Absence from work was associated with the onset of musculoskeletal symptoms (p<0.001), while nurses' financial expenses (out-of-pocket payment) appeared to be associated with the onset of any symptom at 12 months, musculoskeletal symptoms limiting everyday activity at 12 months, and current musculoskeletal symptoms (p=0.001, p=0.002, and p=0.002 respectively). CONCLUSIONS: Musculoskeletal disorders were common among the nursing personnel. Higher levels of stress were related with a higher prevalence of musculoskeletal symptoms.

A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

Advancing athletic assessment by integrating conventional methods with cutting-edge biomedical technologies for comprehensive performance, wellness, and longevity insights.

In modern athlete assessment, the integration of conventional biochemical and ergophysiologic monitoring with innovative methods like telomere analysis, genotyping/phenotypic profiling, and metabolomics has the potential to offer a comprehensive understanding of athletes' performance and potential longevity. Telomeres provide insights into cellular functioning, aging, and adaptation and elucidate the effects of training on cellular health. Genotype/phenotype analysis explores genetic variations associated with athletic performance, injury predisposition, and recovery needs, enabling personalization of training plans and interventions. Metabolomics especially focusing on low-molecular weight metabolites, reveal metabolic pathways and responses to exercise. Biochemical tests assess key biomarkers related to energy metabolism, inflammation, and recovery. Essential elements depict the micronutrient status of the individual, which is critical for optimal performance. Echocardiography provides detailed monitoring of cardiac structure and function, while burnout testing evaluates psychological stress, fatigue, and readiness for optimal performance. By integrating this scientific testing battery, a multidimensional understanding of athlete health status can be achieved, leading to personalized interventions in training, nutrition, supplementation, injury prevention, and mental wellness support. This scientifically rigorous approach hereby presented holds significant potential for improving athletic performance and longevity through evidence-based, individualized interventions, contributing to advances in the field of sports performance optimization.

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma.

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and ß2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.

Gastrointestinal perforations in neonatal period: experience over 10 years.

AIM: This report describes our experience concerning gastrointestinal perforation due to necrotizing enterocolitis during a 10-year period. METHOD: The cases of 27 gastrointestinal perforations, which were treated in our hospital, were retrospectively reviewed. RESULTS: All patients were neonates and infants up to the age of 2 months. The study population consisted of 16 boys (59.3%) and 11 girls (40.7%). Twenty-one neonates (77.8%) were preterm, and the median gestational age was 28 weeks. Twenty-four cases (88.9%) of perforation underwent laparotomy. The overall mortality was 63%. Seventy-six percent of the preterm neonates and only 16.7% of the full-term neonates died. CONCLUSIONS: Gastrointestinal perforation is still connected with a high mortality rate, with necrotizing enterocolitis being the main cause of death. The neonates who did not undergo surgery all died.

In Vivo Estimation of the Biological Effects of Endocrine Disruptors in Rabbits after Combined and Long-Term Exposure: Study Protocol.

Recently, an increasing number of chemical compounds are being characterized as endocrine disruptors since they have been proven to interact with the endocrine system, which plays a crucial role in the maintenance of homeostasis. Glyphosate is the active substance of the herbicide Roundup®, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) are used as plasticizers, while triclosan (TCS), methyl (MePB), propyl (PrPB), and butyl (BuPB) parabens are used as antimicrobial agents and preservatives mainly in personal care products. Studies indicate that exposure to these substances can affect humans causing developmental problems and problems in the endocrine, reproductive, nervous, immune, and respiratory systems. Although there are copious studies related to these substances, there are few in vivo studies related to combined exposure to these endocrine disruptors. The aim of the present pilot study is the investigation and assessment of the above substances' toxicity in rabbits after twelve months of exposure to glyphosate (both pure and commercial form) and to a mixture of all the above substances at subtoxic levels. The lack of data from the literature concerning rabbits' exposure to these substances and the restrictions of the 3Rs Principle will result in a limited number of animals available for use (four animals per group, twenty animals in total).

Antibiotics in Raw Meat Samples: Estimation of Dietary Exposure and Risk Assessment.

The extensive use of antibiotics in livestock farming poses increased concerns for human health as residues of these substances are present in edible tissues. The aim of this study was the determination of the levels of four groups of antibiotics (sulfonamides-SAs, tetracyclines-TCs, streptomycines-STr and quinolones-QNLs) in meat samples (muscles, livers and kidneys from beef, chicken and pork) and the estimation of the dietary exposure to antibiotics from meat consumption and the potential hazard for human health. Fifty-four samples of raw meat were randomly collected in 2018 from the Cretan market, Greece and analyzed both with an enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-mass spectrometry (LC-MS). According to the results derived from the ELISA method, only 2% of the meat samples were free from antibiotics, 2% were detected with 4 antibiotics and the great majority of the samples (87%) were detected with 2 to 3 antibiotics. SAs presented the highest detection frequencies for all samples whereas TCs were not detected in any bovine sample. The highest median concentration was detected for STr in bovine muscles (182.10 µg/kg) followed by QNLs (93.36 µg/kg) in pork kidneys whereas the chicken samples had higher burdens of QNLs compared to the other meat samples. LC-MS analysis showed that oxytetracycline (OTC) was the most common antibiotic in all samples. The highest median concentration of all antibiotics was detected for doxycycline (DOX) (181.73 µg/kg in pork kidney) followed by OTC in bovine liver (74.46 µg/kg). Risk characterization was applied for each of the two methods; The hazard quotients (HQ) did not exceed 0.059 for the ELISA method and 0.113 for the LC-MS method for any group of antibiotics, whereas the total hazard indexes (HI) were 0.078 and 0.021, respectively. The results showed the presence of different groups of antibiotics in meat from the Cretan market and that the health risk to antibiotics is low. A risk assessment analysis conducted for meat consumption and corrected for the aggregated exposure revealed no risk for the consumers.

A comparison of acute hemorrhagic stroke outcomes in 2 populations: the Crete-Boston study.

BACKGROUND AND PURPOSE: Although corticosteroid use in acute hemorrhagic stroke is not widely adopted, management with intravenous dexamethasone has been standard of care at the University Hospital of Heraklion, Crete with observed outcomes superior to those reported in the literature. To explore this further, we conducted a retrospective, multivariable-adjusted 2-center study. METHODS: We studied 391 acute hemorrhagic stroke cases admitted to the University Hospital of Heraklion, Crete between January 1997 and July 2010 and compared them with 510 acute hemorrhagic stroke cases admitted to Massachusetts General Hospital, Boston, from January 2003 to September 2009. Of the Cretan cases, 340 received a tapering scheme of intravenous dexamethasone, starting with 16 to 32 mg/day, whereas the Boston patients were managed without steroids. RESULTS: The 2 cohorts had comparable demographics and stroke severity on admission, although anticoagulation was more frequent in Boston. The in-hospital mortality was significantly lower on Crete (23.8%, n=340) than in Boston (38.0%, n=510; P<0.001) as was the 30-day mortality (Crete: 25.4%, n=307; Boston: 39.4%, n=510; P<0.001). Exclusion of patients on anticoagulants showed even greater differences (30-day mortality: Crete 20.8%; n=259; Boston 37.0%; n=359; P<0.001). The improved survival on Crete was observed 3 days after initiation of intravenous dexamethasone and was pronounced for deep-seated hemorrhages. After adjusting for acute hemorrhagic stroke volume/location, Glasgow Coma Scale, hypertension, diabetes mellitus, smoking, coronary artery disease and statin, antiplatelet, and anticoagulant use, intravenous dexamethasone treatment was associated with better functional outcomes and significantly lower risk of death at 30 days (OR, 0.357; 95% CI, 0.174-0.732). CONCLUSIONS: This study suggests that intravenous dexamethasone improves outcome in acute hemorrhagic stroke and supports a randomized clinical trial using this approach.

Temporal trends and associated factors for pre-hospital and in-hospital delays of stroke patients over a 16-year period: the Athens study.

BACKGROUND: The management and outcome of acute ischemic stroke changed dramatically after the introduction of intravenous thrombolysis. However, relatively few patients have received thrombolytic treatment, mainly due to pre-hospital and/or in-hospital delays. Although the causes of these delays have been adequately studied, their change over a long period has not. METHODS: All acute first-ever stroke patients (n = 2,746) presenting to our academic center from 1993 to 2008 were prospectively documented in a computerized stroke data bank. The time from symptoms onset to presentation at the emergency room and to acquisition of a brain CT was calculated. Time trends over this period as well as the factors affecting them were analyzed. RESULTS: The final study cohort consisted of 2,326 acute stroke patients after excluding 302 patients with an unknown time of stroke onset and 118 who suffered a stroke during hospitalization for another illness. Over the 16-year period, the median time from stroke onset to presentation at the emergency room decreased significantly from 3.15 h (interquartile range 1.30-10.30) to 2.00 h (range 1.00-4.00) (p < 0.001). The median time from emergency room presentation to CT scan completion also decreased significantly (p < 0.001) from 12.3 h (range 4.1-29.8) to 1.0 h (range 0.31-2.77). As a result, the proportion of patients having a CT scan within 4 h of stroke onset increased significantly from 8.6% in 1993-1994 to 53.6% in 2007-2008 (p < 0.001). Thrombolytic treatment was applied in 4.15% of all ischemic stroke patients in the period from 2003 to 2008. Along with other significant factors, use of an emergency medical service was associated with a 57% greater chance of presenting within 3 h after symptoms onset. CONCLUSIONS: These results suggest a continued improvement in pre-hospital and in-hospital delays for stroke management. Public awareness and education regarding medical and paramedical services are necessary for the best early management of acute stroke patients.