Methods and data needs to assess health impacts of chemicals in industrial contaminated sites.

BACKGROUND: human exposure to mixtures of chemicals of toxicological interest, typically found in industrial contaminated sites (ICSs), has been associated with a broad range of different health outcomes. Deprived population groups endure most of the burden of disease and premature death associated to the exposure to those pollutants. Characterising the impacts on health of an ICS is a challenging process. Currently the two main methodological approaches used are Human Health Risk Assessment (HHRA) and Environmental Epidemiological (EE) studies. OBJECTIVES: review existing guidance and scientific evidence for HHRA and EE studies applied to contaminated sites that orientate in selecting the most suitable methodological approach for characterising health impacts in ICSs according to the site characteristics, and the availability of environmental, health and sociodemographic data. RESULTS: HHRA has evolved into a more holistic approach, placing more emphasis in planning, community involvement and adapting the dimension of the assessment to the problem formulation and to the availability of resources. Many different HHRA guidelines for contaminated sites has been published worldwide, and although they share a similar framework, the scientific evidence used for deriving reference values and the variet of policy options can result in a wide variability of health risk estimates. This paper condenses different options with the recommendations to use those tools, default values for environmental and exposure levels and toxicological reference values that most suit to the population and characteristics of the ICSs under evaluation. CONCLUSIONS: the suitability to use one or another approach to assess the impact of ICSs on health depends on the availability of data, cost-benefit aspects and the kind of problem that needs to be answered. Risk assessment based on toxicological data can be very rapid and cheap, providing direct information when the intervention to protect the health of population is urgent and no suitable dose-response functions are available from epidemiological studies. Conducting EE studies provide a deeper insight into the problem of the exposure to industrial pollutants that do not require extrapolation from data obtained from toxicological studies or other population, addressing the community concern's more directly. Complementing the results obtained from different approaches, including those from public health surveillance systems, might provide an efficient and complete response to the impact of ICSs.

Sympathomimetic Toxidromes and Other Pharmacological Causes of Acute Hypertension.

PURPOSE OF REVIEW: Acute drug-induced hypertension, sympathomimetic toxicity, and other hyperadrenergic states can be caused by both xenobiotic toxicity and withdrawal. This manuscript is a selective review of the recent literature regarding pharmacologic causes of hypertensive emergencies and other hyperadrenergic states. RECENT FINDINGS: We will discuss designer stimulants, alpha2 and baclofen agonist withdrawal, and the clinical entity known as posterior reversible encephalopathy syndrome (PRES). Additionally, we examine the controversial "unopposed alpha" phenomenon which may result from use of beta-adrenergic antagonist in the presence of stimulant toxicity. These topics encompass clinical situations and disease entities that are increasingly encountered and are often either unanticipated or under-recognized.

Air Pollution in Kosovo: Short Term Effects on Hospital Visits of Children Due to Respiratory Health Diagnoses.

The Republic of Kosovo is a small country in the Balkans. The capital city of Pristina hosts most of its population and is situated in a mountain basin with poor air exchange, especially during winter. Domestic heating, road transport, industry and coal-fired power plants contribute to high levels of air pollution. We performed a time-series analysis on effects of particulate air pollution (PM2.5) on respiratory health of children and adolescents, using hospital admission and ambulatory visit numbers from the pediatric university clinic. From 2018 until 2020, daily mean concentrations of PM2.5 ranged between 2.41 and 161.03 µg/m³. On average, there were 6.7 ambulatory visits per day with lower numbers on weekends and during the first COVID-19 wave in 2020. An increase in PM2.5 led to an immediate increase in visit numbers that lasted over several days. Averaged over a full week, this amounted to about a 1% increase per 10 µg/m³. There were, on average, 1.7 hospital admissions per day. Two and three days after a rise in air pollution, there was also a rise in admission numbers, followed by a decline during the consecutive days. This might indicate that the wards were overstressed because of high admission numbers and restricted additional admissions.

Citizens' Perception and Concerns on Chemical Exposures and Human Biomonitoring-Results from a Harmonized Qualitative Study in Seven European Countries.

Exposure to different chemicals is an inevitable part of our everyday lives. Within HBM4EU, focus group discussions were conducted to gather data on citizens' perceptions of chemical exposure and human biomonitoring. These discussions were hosted in Cyprus, Denmark, Hungary, Israel, Latvia, the Netherlands, and North Macedonia following a protocol developed in the first round of discussions. Results indicate the very high concern of European citizens regarding food safety and the environment. Focus group participants were well aware of potential uptake of chemicals through food consumption (e.g., preservatives, flavor enhancers, coloring agents, pesticides, fertilizers, metals), drinking water, or from polluted air and water. One of the positive aspects identified here, is the high interest of citizens in awareness and education on personal measures to control exposure. The promotion of personal behavioral changes requires active involvement of society (e.g., commuting habits, energy choices, waste disposal, dietary habits). Activities should focus on raising awareness of the general public, implementation of policy measures, and mainstreaming of related topics into the education system. Raising awareness of the general public may promote engagement of citizens, which in turn may empower them to put pressure on politicians to take effective actions. There is also a need for further research which might focus on the impact of country-specific situations and of the COVID-19 pandemic on the exposure of citizens to chemicals.

Losing Years of Human Life in Heavy Polluted Cities in Macedonia.

INTRODUCTION: The urban air pollution will deteriorate globally, by 2050 outdoor particulate air pollution and ground-level ozone is projected to become the top cause of environmentally related deaths worldwide. AIM: To assess the burden of diseases due to particulate air pollution and health benefits form the pollution reduction policies. METHODS: Environmental burden of disease methodology has been applied. Environmental data for population exposure, total years of life lost from all causes, and relevant concentration-response functions have been used in estimation. RESULTS: The estimated disease burden from all causes (excl. external) is 30,256 YLL (19,436-40,625 95% CI) in Skopje Region, and 10,343 YLL (6,224-14,785 95% CI) in Tetovo. In terms of cardiopulmonary mortality, the estimated disease burden is 9,282/100,000 in Tetovo, in the Skopje Region 3,784/100,000 respectively. Annually in Tetovo 1,645 years of healthy life are lost, while in the Skopje Region 3,936 due to lung cancer premature mortality. The estimated health gain is significant, for the three selected health outcomes if EU limit values are reached, 41-42% of the estimated burden in Skopje Region will be eliminated, and 74-77% in Tetovo. CONCLUSION: the estimated impact of particulate air pollution on mortality is significant and not negligible. The same applies to the health and well-being of the population if the EU or WHO limit levels are reached.

How Good Is our Place-Implementation of the Place Standard Tool in North Macedonia.

This study describes the implementation, in North Macedonia, of a "tool", initially devised in Scotland, to generate community and stakeholder discussion about the places in which they live and notably a place's capacity to generate health wellbeing and greater equity among citizens. In this study, the "place standard tool" (PST) is viewed from the perspective of creating places which can deliver a triple win of health and wellbeing, equity, and environmental sustainability. Skopje, North Macedonia's capital, inevitably differs economically, culturally, and politically from Scotland, thus providing an opportunity to augment existing knowledge on adaptability of the tool in shaping agendas for policy and action. Тhe PST was tested through seminars with selected focus groups and an online questionnaire. Over 350 respondents were included. Information on priorities enabled the distillation of suggestions for improvement and was shared with the Mayor and municipal administration. Skopje citizens valued an approach which solicited their views in a meaningful way. Specific concerns were expressed relating to heavy traffic and related air and noise pollution, and care and maintenance of places and care services. Responses varied by geographic location. Application of the PST increased knowledge and confidence levels among citizens and enthusiasm for active involvement in decision making. Effective implementation relies heavily on: good governance and top-level support; excellent organization and good timing; careful training of interviewers and focus group moderators; and on prior knowledge of the participants/respondents.

Re-evolution of the 2-phenylquinolines: ligand-based design, synthesis, and biological evaluation of a potent new class of Staphylococcus aureus NorA efflux pump inhibitors to combat antimicrobial resistance.

Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.

From 6-aminoquinolone antibacterials to 6-amino-7-thiopyranopyridinylquinolone ethyl esters as inhibitors of Staphylococcus aureus multidrug efflux pumps.

The thiopyranopyridine moiety was synthesized as a new heterocyclic base to be inserted at the C-7 position of selected quinolone nuclei followed by a determination of antibacterial activity against strains of Staphylococcus aureus. Selected thiopyranopyridinylquinolones showed significant antimicrobial activity, including strains having mutations in gyrA and grlA as well as other strains overexpressing the NorA multidrug (MDR) efflux pump. Most derivatives did not appear to be NorA substrates. The effect of the thiopyranopyridinyl substituent on making these quinolones poor substrates for NorA was investigated further. Several quinolone ester intermediates, devoid of any intrinsic antibacterial activity, were tested for their abilities to inhibit the activities of NorA (MFS family) and MepA (MATE family) S. aureus MDR efflux pumps. Selected quinolone esters were capable of inhibiting both MDR pumps more efficiently than the reference compound reserpine. Moreover, they also were able to restore, and even enhance, the activity of ciprofloxacin toward some genetically modified resistant S. aureus strains.