Human Health Effects of Oral Exposure to Chromium: A Systematic Review of the Epidemiological Evidence.

The toxicity and carcinogenicity of hexavalent chromium via the inhalation route is well established. However, a scientific debate has arisen about the potential effects of oral exposure to chromium on human health. Epidemiological studies evaluating the connection between ingested chromium and adverse health effects on the general population are limited. In recent years, a wealth of biomonitoring studies has emerged evaluating the associations between chromium levels in body fluids and tissues and health outcomes. This systematic review brings together epidemiological and biomonitoring evidence published over the past decade on the health effects of the general population related to oral exposure to chromium. In total, 65 studies were reviewed. There appears to be an inverse association between prenatal chromium exposure and normal fetal development. In adults, parameters of oxidative stress and biochemical alterations increase in response to chromium exposure, while effects on normal renal function are conflicting. Risks of urothelial carcinomas cannot be overlooked. However, findings regarding internal chromium concentrations and abnormalities in various tissues and systems are, in most cases, controversial. Environmental monitoring together with large cohort studies and biomonitoring with multiple biomarkers could fill the scientific gap.

General practitioners' views towards management of common mental health disorders: Τhe critical role of continuing medical education.

BACKGROUND: The disability burden of common mental health disorders is enormous and should be faced at the first point of contact in the healthcare system. General Practitioners (GPs) are called to recognize, diagnose, and manage patients with mental health disorders, a task which is not always addressed successfully. The study aims at examining the relationship between mental health education of GPs and self-reported opinions on the care they provide to patients with mental disorders in Greece. METHODS: A questionnaire investigating GPs' viewpoints regarding diagnostic methods, referral rates and overall management of patients with mental disorders, and how these are impacted by their education on mental health, was employed, in a randomly selected sample of 353 GPs in Greece. Suggestions and proposals about improvement of ongoing mental health training, along with organizational reforming were also recorded. RESULTS: Received Continuing Medical Education (CME) is characterized as insufficient by 56.1% of the GPs. More than half of the GPs participate in clinical tutorials and mental health conferences once per three years or less. The level of educational score on mental health is associated positively with decisiveness on management of patients and increases self-confidence. A percentage of 77.6% states knowledge of the appropriate treatment and 56.1% agree to initiate treatment without referring to a specialist. However, low to moderate self-confidence about diagnosis and treatment is stated by 47.5%. According to GPs, critical points for improving mental health primary care are the liaison psychiatry and high degree of CME. CONCLUSION: Greek GPs are calling for focused and continuing medical education, in the field of psychiatry, along with essential structural and organizational reforming of the healthcare system, including an efficient liaison psychiatry.

In Vitro Anti-Biofilm Activity of Bacteriophage K (ATCC 19685-B1) and Daptomycin against Staphylococci.

The purpose of the present study was to investigate anti-staphylococcal activity of daptomycin and bacteriophage K, alone or in combination, against biofilm-producers and non-producers S. aureus and S. epidermidis strains, under biofilm forming and cells' proliferation conditions. Daptomycin and bacteriophage K (ATCC 19685B1), in different concentrations, were tested against 10 Staphylococcus aureus and 10 S. epidermidis, characterized by phenotypes and genotypes. The quantitative microtiter plate (crystal violet, CV), methylthiazoltetrazolium (MTT), and growth curve (GC) assays were performed. No statistically significant difference was found between species, whereas daptomycin alone performed better using medium and high concentrations of the drug and bacteriophage K was more active against strains with higher susceptibility, by CV and MTT assays. Best results were achieved using both agents combined in high concentrations. Bacteriophage K was effective within 3.8 and 2.4 h, depending on the concentration used, by the GC assay. Combination of daptomycin with bacteriophage K was more effective against staphylococci, depending on the concentrations used and strains' susceptibility. Further studies are needed to evaluate if this approach might be a choice for prevention or therapy of biofilm-associated infections.

Prevalence and associated factors of anxiety and depression in students at a Greek university during COVID-19 lockdown.

BACKGROUND: Restrictions on movement and lockdown are measures taken in many nations, in response to the COVID-19 pandemic. University students are additionally burdened by the transition to distance e-learning. The aims of the study were to investigate the prevalence of anxiety and depression in university students and to identify associated risk factors. DESIGN AND METHODS: An online questionnaire was administered to 2,009 students in the University of Patras, Greece, during the national lockdown. Socio-demographic, academic data, and the forced disruption of daily life were assessed along with the Greek version of the Hospital Anxiety and Depression Scale. RESULTS:  Anxiety and depression prevalence was 35.8% and 51.2% respectively. Age, school of study, financial status, self-perceived health status, level of satisfaction with the state's and university's response and specific aspects in the daily routine were associated with both anxiety and depression scores. At higher odds of both depression and anxiety were students with low income, bad health status, annoyed at staying home and those who encountered difficulties with the online education system. Additional risk factors for depression were studies in humanities and social sciences, and low satisfaction with the university's response, while for anxiety were studies in agricultural sciences and absence of information about COVID-19. CONCLUSIONS: The proportion of Greek students showing depression and anxiety, during the restrictive measures, is alarming. Mental health in university students should be monitored. Mitigation strategies should focus on specific personal, academic and social variables that have been identified as protective factors.

Oxidative Damage of Mussels Living in Seawater Enriched with Trace Metals, from the Viewpoint of Proteins Expression and Modification.

The impact of metals bioaccumulation in marine organisms is a subject of intense investigation. This study was designed to determine the association between oxidative stress induced by seawater enriched with trace metals and protein synthesis using as a model the mussels Mytilus galloprovincialis. Mussels were exposed to 40 µg/L Cu, 30 µg/L Hg, or 100 µg/L Cd for 5 and 15 days, and the pollution effect was evaluated by measuring established oxidative biomarkers. The results showed damage on the protein synthesis machine integrity and specifically on translation factors and ribosomal proteins expression and modifications. The exposure of mussels to all metals caused oxidative damage that was milder in the cases of Cu and Hg and more pronounced for Cd. However, after prolonged exposure of mussels to Cd (15 days), the effects receded. These changes that perturb protein biosynthesis can serve as a great tool for elucidating the mechanisms of toxicity and could be integrated in biomonitoring programs.

New Chloramphenicol Derivatives from the Viewpoint of Anticancer and Antimicrobial Activity.

Over the last years, we have been focused on chloramphenicol conjugates that combine in their structure chloramphenicol base with natural polyamines, spermine, spermidine and putrescine, and their modifications. Conjugate 3, with spermidine (SPD) as a natural polyamine linked to chloramphenicol base, showed the best antibacterial and anticancer properties. Using 3 as a prototype, we here explored the influence of the antibacterial and anticancer activity of additional benzyl groups on N1 amino moiety together with modifications of the alkyl length of the aminobutyl fragment of SPD. Our data demonstrate that the novel modifications did not further improve the antibacterial activity of the prototype. However, one of the novel conjugates (4) showed anticancer activity without affecting bacterial growth, thus emerging as a promising anticancer agent, with no adverse effects on bacterial microflora when taken orally.

Oxidative damage of 18S and 5S ribosomal RNA in digestive gland of mussels exposed to trace metals.

Numerous studies have shown the ability of trace metals to accumulate in marine organisms and cause oxidative stress that leads to perturbations in many important intracellular processes, including protein synthesis. This study is mainly focused on the exploration of structural changes, like base modifications, scissions, and conformational changes, caused in 18S and 5S ribosomal RNA (rRNA) isolated from the mussel Mytilus galloprovincialis exposed to 40µg/L Cu, 30µg/L Hg, or 100µg/L Cd, for 5 or 15days. 18S rRNA and 5S rRNA are components of the small and large ribosomal subunit, respectively, found in complex with ribosomal proteins, translation factors and other auxiliary components (metal ions, toxins etc). 18S rRNA plays crucial roles in all stages of protein synthesis, while 5S rRNA serves as a master signal transducer between several functional regions of 28S rRNA. Therefore, structural changes in these ribosomal constituents could affect the basic functions of ribosomes and hence the normal metabolism of cells. Especially, 18S rRNA along with ribosomal proteins forms the decoding centre that ensures the correct codon-anticodon pairing. As exemplified by ELISA, primer extension analysis and DMS footprinting analysis, each metal caused oxidative damage to rRNA, depending on the nature of metal ion and the duration of exposure. Interestingly, exposure of mussels to Cu or Hg caused structural alterations in 5S rRNA, localized in paired regions and within loops A, B, C, and E, leading to a continuous progressive loss of the 5S RNA structural integrity. In contrast, structural impairments of 5S rRNA in mussels exposed to Cd were accumulating for the initial 5days, and then progressively decreased to almost the normal level by day 15, probably due to the parallel elevation of metallothionein content that depletes the pools of free Cd. Regions of interest in 18S rRNA, such as the decoding centre, sites implicated in the binding of tRNAs (A- and P-sites) or translation factors, and areas related to translation fidelity, were found to undergo significant metal-induced conformational alterations, leading either to loosening of their structure or to more compact folding. These modifications were associated with parallel alterations in the translation process at multiple levels, a fact suggesting that structural perturbations in ribosomes, caused by metals, pose significant hurdles in translational efficiency and fidelity.

Hair biomonitoring and health status of a general population exposed to Nickel.

An epidemiological cross-sectional study was conducted in a Greek population, being orally exposed to Ni via food consumption, in order to investigate possible health effects and to evaluate hair Ni concentration as a biomarker of exposure. The study population consisted of 139 men and 155 women, aged 25-69. Socio-demographics, lifestyle, dietary habits, occupational and medical history data were recorded through a personal interview. Hematological and biochemical examinations were conducted in blood specimens. Metals - Ni, Cr, Cd, Pb, Hg, Cu and Zn - were determined in hair samples. Women were characterized by higher Ni and Cu hair concentrations, while men by higher Cr and Hg. Factors affecting hair metal concentrations were identified to be dietary habits, consumption of local crops, occupation and smoking. Hair element content in the study population was comparable to the "reference ranges" reported in Europe, except for Ni, found higher in a fraction of our population. Men in the upper quartile of hair Ni distribution are at higher risk for abnormal high cholesterol, LDL, albumin and calcium, with odds ratios (OR) varying between 3.5 and 6.2. Accordingly, high hair Ni content in women is associated with abnormal glucose (OR=3.9), triglycerides (OR=3.1) and low abnormal sodium (OR=4.3). The study provides evidence of the suitability of hair analysis in assessing environmental exposure to Ni and supports the use of hair Ni content as a valuable and relatively inexpensive tool of biomonitoring, to identify people at risk for certain biochemical alterations.

Arsenic and antimony removal from drinking water by adsorption on granular ferric oxide.

Arsenic and antimony occur in drinking water due to natural weathering or anthropogenic activities. There has been growing concern about their impact on health. The aim of this study was to assess the efficiency of a granular ferric oxide adsorbent medium to remove arsenic and antimony from drinking water via rapid small-scale column tests (RSSCTs). Three different water matrices - deionized, raw water treated with a reverse osmosis domestic device and raw water - were spiked with arsenic and/or antimony to a concentration of 100 µg L⁻¹. Both elements were successfully adsorbed onto the medium. The loadings until the guideline value was exceeded in the effluent were found to be 0.35-1.63 mg g⁻¹ for arsenic and 0.12-2.11 mg g⁻¹ for antimony, depending on the water matrix. Adsorption of one element was not substantially affected by the presence of the other. Aeration did not affect significantly the adsorption capacity. Granular ferric oxide could be employed for the simultaneous removal of arsenic and antimony from drinking water, whereas full-scale systems should be assessed via laboratory tests before their implementation.

Chromium in drinking water: association with biomarkers of exposure and effect.

An epidemiological cross-sectional study was conducted in Greece to investigate health outcomes associated with long-term exposure to chromium via drinking water. The study population consisted of 304 participants. Socio-demographics, lifestyle, drinking water intake, dietary habits, occupational and medical history data were recorded through a personal interview. Physical examination and a motor test were carried out on the individuals. Total chromium concentrations were measured in blood and hair of the study subjects. Hematological, biochemical and inflammatory parameters were determined in blood. Chromium in drinking water ranged from <0.5 to 90 µg·L-1 in all samples but one (220 µg·L-1), with a median concentration of 21.2 µg·L-1. Chromium levels in blood (median 0.32 µg·L-1, range <0.18-0.92 µg·L-1) and hair (median 0.22 µg·g-1, range 0.03-1.26 µg·g-1) were found within "normal range" according to the literature. Personal lifetime chromium exposure dose via drinking water, calculated from the results of the water analyses and the questionnaire data, showed associations with blood and hair chromium levels and certain hematological and biochemical parameters. Groups of subjects whose hematological or biochemical parameters were outside the normal range were not correlated with chromium exposure dose, except for groups of subjects with high triglycerides or low sodium. Motor impairment score was not associated with exposure to chromium.

Does farming have an effect on health status? A comparison study in west Greece.

Investigating the health status of agricultural workers is a challenging goal. Contradictory outcomes concerning farmers' health are reported in the literature. In this cross-sectional study, certain clinical and neurobehavioral health outcomes were compared between farmers and non-farmers living in the same rural area. Farmers (328) and non-farmers (347), matched per age and sex, were selected randomly in an agricultural area in West Greece. Both groups underwent haematological and biochemical examinations and were administered two neurobehavioral tests, namely the Mini-Mental State Examination (MMSE) and the Montgomery-Åsberg Depression Rating Scale (MADRS). Sociodemographic, personal medical, nutritional and lifestyle data were recorded. According to personal statements, farmers suffered from hypertension, cardiovascular, orthopaedic and ENT problems in higher frequency. Haematocrit, haemoglobin and serum cholinesterase's activity were found to be lower among farmers. Lower prevalence of hypertension and better performances on MMSE and MADRS tests were recorded in young farmers in relation to young non-farmers, while these findings were reversed in older ages. Odds Ratios were calculated through multivariate logistic regression models. Factors affecting these impairments remain to be clarified.

Interrelationships of pollution load index, transfer factor, and concentration factor under the effect of sludge.

A greenhouse experiment was conducted during 2010-2011. A complete randomized blocks design was used including seven treatment levels of sludge(tons per hectare), i.e., 0, 6, 12, 18, 24, 30, and "30+ treated wastewater", in four replications. Lettuce (Lactuca sativa L var longifolia) was chosen as a test plant. The purpose of the experiment was to study the relationships between soil Pollution Load Index, heavy metal transfer factor, and concentration factor and to determine optimum concentration factor values. The following were found: several mathematical relationships were established between the above parameters that could be used for the study of heavy metal accumulation in soils and plants under the effect of the applied sludge. They can be also used for the calculation of one of the above parameters as a function of the others. Based on the experimental data, the optimum concentration factor for several heavy metals were determined by multiple linear regression analysis, expressing the concentration factor as a function of the maximum dry lettuce matter yield, and of optimum/minimum heavy metal content of plant dry matter. The mean value of the calculated concentration factor obtained for each separate metal was: Zn, 2.93; Cd, 0.39; Co, 1.47; and Ni, 0.52.

Translational responses and oxidative stress of mussels experimentally exposed to Hg, Cu and Cd: one pattern does not fit at all.

Certain metals, like Hg, Cu and Cd, are capable of down-regulating protein synthesis in several marine organisms, including Mytilus galloprovincialis. Nevertheless, due to the complexity of the environmental stress, it is difficult to evaluate the influence of individual metals on protein synthesis via field studies. To bypass this difficulty, experimental studies were carried out on M. galloprovincialis exposed in aquarium for 15 days to one of three selected metal salts, HgCl(2), CuCl(2) and CdCl(2). Polysome profile was determined in digestive gland extracts of the exposed mussels as a way of measuring the functional status of ribosomes, superoxide radical production and lipid peroxidation as indicators of oxidative stress, metallothionein content as a metal detoxification index, and superoxide dismutase activity as a free radicals-scavenging index. Exposure of mussels to Hg(2+) or Cu(2+) resulted in a concentration- and time-dependent decrease in the polysome content of digestive gland cells, which at 15th day of exposure and at the highest metal concentrations tested, was 32% and 19% of the control, respectively. Both metals, at the concentrations used (<40 µg/L), did not significantly influence the oxidative stress biomarkers. By contrast, Cd(2+) treatment significantly induced superoxide radical production and lipid peroxidation in digestive gland cells, hinting that mussels suffered from oxidative stress. Polysome levels in Cd(2+)-exposed mussels were initially decreased by day 5 in digestive gland cells and then elevated to reach nearly the control levels by 15 days of exposure. Elevated protein synthesis was associated with significantly increased production of metallothioneins, whereas such increase was not recorded in Hg(2+)- or Cu(2+)-exposed mussels. Interestingly, the ribosome efficiency at initiating protein synthesis followed a similar pattern of polysome alterations, a fact suggesting that regulation of protein synthesis mainly occurred at the initiation phase of translation. Overall, these results suggest that the effect of each metal on protein synthesis is idiosyncratic and depends on its ability to induce specific cellular defense mechanisms against oxidative stress.

Assessing quality of raw milk in southern Greece in the aspect of certain benzimidazole residues.

Benzimidazoles are veterinary drugs widely used against endoparasites in food-producing animals. Albendazole (ABZ), a benzimidazole, is believed to cause embryotoxicity, teratogenicity and other adverse health effects. This study assessed the residue levels of ABZ and its two major metabolites, the sulfoxide (ABZ-SO) and sulfone (ABZ-SO2), in raw milk samples collected from farms in southern Greece during the spring and autumn of 2008. Analysis was performed by HPLC using a diode array detector. A total of 16% of the 89 samples examined were positive for ABZ metabolites in the range 11-70 ng ml(-1), but the parent compound was not detected in any sample. A geographical variation in positive samples was observed, but season or milk type (ovine, bovine, goat) was unrelated to the presence of residues. Considering the lipophilic character of these substances and the possibility of higher concentrations in dairy foods, we suggest greater controlled usage of these drugs.

Translational responses of Mytilus galloprovincialis to environmental pollution: integrating the responses to oxidative stress and other biomarker responses into a general stress index.

Heavy metals are commonly associated with the generation of reactive oxygen species (ROS), which may cause oxidative damage to several cellular macromolecules and organelles. In an attempt to correlate biomarker responses to oxidative stress, caged mussels (Mytilus galloprovincialis) were exposed for 30 days in a relatively clean site and two areas (Stations 1 and 2) unevenly polluted by heavy metals in Gulf of Patras (Greece). Three periods of caging were: one in winter, the second in spring, and the third in autumn. Heavy metal content was determined in digestive glands of the exposed mussels as a measure of metal pollution, metallothionein content as an adaptive and detoxifying index, lysosomal membrane stability as a biomarker of general stress, superoxide radical production and lipid peroxidation as indicators of oxidative stress, and micronucleus frequency in gill cells as an index of chromosomal damage. Considering that protein-synthesizing machinery is one of the candidate targets for ROS, the in vivo activity of ribosomes in digestive glands was also tested. Compared with the reference samples, mussels transplanted to Station 1 showed increased levels of heavy metals and metallothionein in digestive glands, lower lysosomal membrane stability, higher values in oxidative stress indices, reduced activity of ribosomes, and increased chromosomal damage in gill cells. In addition, run-off ribosomes isolated from mussels transplanted to Station 1 were less efficient at initiating protein synthesis in a cell-free system than those from mussels in the reference site. Mussels transplanted to Station 2 exhibited similar but less pronounced responses. Statistical analysis revealed a strong positive correlation of ribosomal activity with lysosomal membrane stability, as well as a significant negative correlation with the oxidative stress indices, metallothionein content, micronucleus frequency, and the digestive gland content in Cr, Cu and Mn. Integration of all the measured biomarker responses into one general "stress index" demonstrated a clear distinction between the sampling sites, allowing classification along a pollution gradient (reference site

Evaluating contamination of dredges and disposal criteria in Greek coastal areas.

Sediments were collected from areas that were going to be dredged located at six small Greek ports, as well as from possible disposal areas. In order to assess the contamination level of dredged material, the samples were analysed for pH, organic matter, the metals Cd, Pb, Hg, Cr, Ni, Cu, Zn and major organic compounds (PAHs, PCBs). The sediments' quality was evaluated by two approaches: (i) by classifying each area according to two sets of Sediment Quality Guidelines (SQGs) and (ii) by calculating the contamination factors and degree for each area. The results showed that organic compounds were detected in trace amounts in 14% of the port samples belonging to the PAHs group. The characterization of the sediment samples was based on the metals' concentration showing that the majority of the areas to be dredged (80%) are classified as of medium-low contamination according to the SQGs. However, according to the contamination degree, only 30% of the areas are classified as of low contamination, while 40% as of moderate contamination and 30% of the areas as of considerable contamination. From the point of view of "no disturbance" of the ecosystem, decisions about dumping should be taken only after evaluating the material to be dredged. If the SQGs are exceeded, dumping must be forbidden. Otherwise, further evaluation is needed based on the comparison with the receiving area, i.e. by estimating the contamination degree. Dumping could be allowed if the contamination degree is found to be below moderate.

Evaluation of the global protein synthesis in Mytilus galloprovincialis in marine pollution monitoring: seasonal variability and correlations with other biomarkers.

Protein synthesis down-regulation is a life-saving mechanism for many organisms exposed to xenobiotics that threaten normal life. The present study was designed to assess the spatial and seasonal variability of global protein synthesis, determined in the microsomal fraction of digestive glands from caged Mytilus galloprovincialis mussels exposed for 30 days in a relatively clean region and two unevenly polluted areas (Stations 1 and 2) along the Gulf of Patras (Greece). The in vivo activity of translating ribosomes was evaluated by analyzing the translating ribosomes, polysome content, which may serve as an indicator of the efficiency of the protein-synthesizing machinery. To correlate with classical biomonitoring strategies, various biomarkers were measured in digestive glands, including metallothionein content, heavy-metal content, and lysosomal membrane stability. In parallel, gill cells were examined for micronucleus frequency. Metal ion concentrations were also estimated in the surrounding waters as a measure of metal exposure. Substantially lower polysome content was recorded in caged mussels collected from Station 1, in particular during the winter and spring sampling. As verified by chemical analysis of the seawater and measurement of other biomarkers, Station 1 was more contaminated than Station 2. Polysome content was found negatively correlated with metallothionein levels, micronucleus frequency and cytosolic Cu and Hg in all seasons. In addition, negative correlations were obtained between polysome content and lysosomal membrane stability in winter and spring. A progressive increase in polysomes was observed from winter to autumn, in particular in samples from Station 1. A non-uniform trend was detected in 80S ribosomal monosomes, whereas the seasonal changes in ribosomal subunits were opposite to those found in polysome content. Comparisons between seasonal and local site-specific influences on polysome content provides evidence that winter and spring are the most appropriate sampling seasons for application of translation activity as a possible biomarker in biomonitoring studies.

PFGE analysis of enterococci isolates from recreational and drinking water in Greece.

Biotyping and DNA fingerprinting by pulsed-field gel electrophoresis were applied to a collection of enterococci recovered from recreational and drinking water, in order to identify possible genetic relationships. Clinical strains of hospital origin were compared to the environmental isolates. A total of 104 enterococci were isolated from 128 recreational water (94 marine and 34 river water) and 470 drinking water supplies (440 municipal and 30 natural spring water samples). Sixty-two isolates were characterised as Enterococcus faecium recovered from all sources, 32 E. faecalis (from all sources), 4 E. durans (from marine, river and municipal water), 4 E. gallinarum (from marine water) and 2 E. avium (from marine and municipal water). Biotypes, determined with API20Strep, among E. faecium were correlated with certain environmental sources, while antibiotypes, determined with Etest, did not reveal any relationship to the sample origin. Even though genetic diversity was observed among the studied strains, common clonal types were also identified in different sources, suggesting a possible common origin of the enterococci. Cluster analysis revealed a genetic relationship between certain environmental E. faecium and clinical strains.