Editorial: The society for environmental geochemistry and health (SEGH): 50 years and beyond.

When the SEGH international board released a short editorial paper back in 2019, we described an aim to increase the membership offering, whilst improving the diversity of input regionally, by scientific discipline and to ensure greater and more regular contact across the regions from 2020 onwards. Wider aspirations described in 2019 (Watts et al. 2019) are discussed within this short communication at the end of 2021 to evaluate progress made. In particular, how the SEGH community adapted to the unprecedented circumstances that have challenged each and every one of us throughout the COVID-19 pandemic since early 2020 and are likely to influence our activities for the foreseeable future.

AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.

BACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds.

The potential impact of geological environment on health status of residents of the Slovak Republic.

In order to assess the potential impact of the geological environment on the health of the population of the Slovak Republic, the geological environment was divided into eight major units: Paleozoic, Crystalline, Carbonatic Mesozoic and basal Paleogene, Carbonatic-silicate Mesozoic and Paleogene, Paleogene Flysch, Neovolcanics, Neogene and Quaternary sediments. Based on these geological units, the databases of environmental indicators (chemical elements/parameters in groundwater and soils) and health indicators (concerning health status and demographic development of the population) were compiled. The geological environment of the Neogene volcanics (andesites and basalts) has been clearly documented as having the least favourable impact on the health of Slovak population, while Paleogene Flysch geological environment (sandstones, shales, claystones) has the most favourable impact. The most significant differences between these two geological environments were observed, especially for the following health indicators: SMRI6364 (cerebral infarction and strokes) more than 70 %, SMRK (digestive system) 55 %, REI (circulatory system) and REE (endocrine and metabolic system) almost 40 % and REC (malignant neoplasms) more than 30 %. These results can likely be associated with deficit contents of Ca and Mg in groundwater from the Neogene volcanics that are only about half the level of Ca and Mg in groundwater of the Paleogene sediments.

Characterization of Santa Catarina (Brazil) coal with respect to human health and environmental concerns.

The current paper presents the concentration, distribution, and modes of occurrence of trace elements of 13 coals from south Brazil. The samples were collected in the state of Santa Catarina. Chemical analyses and the high ash yields indicate that all studied coals are rich in mineral matter, with SiO(2) and Al(2)O(3) dominating as determined by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Quartz is the main mineral species and is associated with minor levels of feldspars, kaolinite, hematite, and iron-rich carbonates. The contents of trace elements, including As, Pb, Cd, Ni, Cr, Mn, Be, V, U, Zn, Li, Cu, Tl, and Ni, in coals were determined. A comparison of ranges and means of elemental concentrations in Santa Catarina, Brazil, and world coals shows that the ranges of most elements in Santa Catarina coal are very close to the usual worldwide concentration ranges in coal.

The studying of washing of arsenic and sulfur from coals having different ranges of arsenic contents.

To study the effectiveness of washing in removal of arsenic and sulfur from coals with different ranges of arsenic concentration, coal was divided into three groups on the basis of arsenic content: 0-5.5 mg/kg, 5.5 mg/kg-8.00 mg/kg, and over 8.00 mg/kg. The result shows that the arsenic in coals with higher arsenic content occurs mainly in an inorganic state and can be relatively easily removed. Arsenic removal is very difficult and less complete when the arsenic content is lower than 5.5 mg/kg because most of this arsenic is in an organic state. There is no relationship between washing rate of total sulfur and arsenic content, but the relationship between the washing rate of total sulfur and percent of organic sulfur is very strong.

[Content and distribution of fluorine in Chinese coals].

Nationwide sampling program is designed according to the resources distribution and coal-forming periods as well as coal rank and yield of coal in China, and 305 coal samples were collected from 26 provinces, municipalities and autonomous regions. Fluorine in coal is determined by pyrohydrolysis / fluoride-ion selective electrode method. Fluorine in coals is mainly of an inorganic nature. Coal rank has no effect on fluorine content. The influence of a factor, such as geological age, on fluorine contents might be concealed by other factors, more research should be done to discern it. The distribution of fluorine in each province, municipality and autonomous region's coals is studied, and the fluorine source in coal-burning endemic fluorosis areas should be estimated over again. The contents of fluorine in Chinese coals show logarithm normal distribution, and 90% of values ranged from 47mg/kg to 347mg/kg, the average fluorine content in Chinese coals was designated as the geometric mean, 136mg/kg. Fluorine in Chinese coals is within the world coal's range.

An economic evaluation of a chlorhexidine chip for treating chronic periodontitis: the CHIP (chlorhexidine in periodontitis) study.

BACKGROUND: The authors previously suggested that an adjunctive, controlled-release chlorhexidine, or CHX, chip may reduce periodontal surgical needs at little additional cost. This article presents an economic analysis of the CHX chip in general dental practice. METHODS: In a one-year prospective clinical trial, 484 chronic periodontitis patients in 52 general practices across the United States were treated with either scaling and root planing, or SRP, plus any therapy prescribed by treating, unblinded dentists; or SRP plus other therapy as above but including the CHX chip. Economic data were collected from bills, case report forms and 12-month treatment recommendations from blinded periodontist evaluators. RESULTS: Total dental charges were higher for SRP + CHX chip patients vs. SRP patients when CHX chip costs were included (P = .027) but lower when CHX chip costs were excluded (P = .012). About one-half of the CHX chip acquisition cost was offset by savings in other charges. SRP + CHX chip patients were about 50 percent less likely to undergo surgical procedures than were SRP patients (P = .021). At the end of the trial, periodontist evaluators recommended similar additional procedures for both groups: SRP, about 46 percent; maintenance, about 37 percent; surgery, 56 percent for SRP alone and 63 percent for SRP + CHX chip. CONCLUSIONS: Adjunctive CHX chip use for general-practice patients with periodontitis increased costs but reduced surgeries over one year. At study's end, periodontists recommended similar additional surgical treatment for both groups. CLINICAL IMPLICATIONS: In general practice, routine use of the CHX chip suggests that costs will be partially offset by reduced surgery over at least one year.

Using the PerioChip in treating adult periodontitis: an interim report.

Multicenter clinical trials have established that the adjunctive use of the subgingival controlled release of chlorhexidine, in the form of the PerioChip, significantly reduces pocket probing depth, improves probing attachment levels, and reduces bleeding on probing compared to scaling and root planing alone, for periods up to 9 months. The purpose of the present study was to report on the adjunctive use of the PerioChip for the long-term management of adult periodontitis for 2 years. A total of 836 patients with adult periodontitis from private dental offices were recruited into the trial. This interim report is on the first 72 patients to have completed the 2-year study. Treatments included initial definitive therapy followed by PerioChip placement in pocket sites with a pocket probing depth of > or = 5 mm after 1 month. Subsequently, the patients received routine periodontal maintenance therapy together with the placement of a PerioChip in pockets with pocket probing depths > or = 5 mm every 3 months. Results indicated that there was a continuous decrease in pocket probing depth over the 2 years (1.26 +/- 0.77 mm). This decrease in pocket probing depth was marked over the first 9 to 12 months, and then appeared to be less marked over the next 12 months. At 2 years, 60% of the patients had at least 2 pockets showing a reduction of 2 mm or more, and only 10% of the patients showed no change or increased pocket probing depth. The results indicate that adjunctive PerioChip use is a clinically effective treatment option for dental professionals and their patients for the long-term management of adult periodontitis.

The cost-effectiveness of a new chlorhexidine delivery system in the treatment of adult periodontitis.

BACKGROUND: Periodontal treatment is costly. The authors assessed the potential economic impact of a new periodontal chemotherapeutic, testing the hypothesis that its adjunctive use would result in reduced periodontal surgical needs. METHODS: An economic model estimated treatment needs following two clinical trials of the adjunctive use of a chlorhexidine, or CHX, -containing chip compared with scaling and root planing, or SRP, alone. Needs were based on periodontal status at nine months and a probabilistic algorithm; costs were assigned on the basis of a national dental survey and an average wholesale price of the CHX chip. RESULTS: The base case model projected significantly more maintenance procedures and significantly fewer periodontal surgical procedures for patients treated with SRP and the CHX chip compared with patients who were treated with SRP alone (54.4 percent vs. 46.4 percent, P = .014; 29.2 percent vs. 35.5 percent, P = .015, respectively). Average total costs of care for patients treated with SRP and CHX chip were $737 +/- $244 compared with $734 +/- $239 for patients treated with SRP alone. Sensitivity analyses to account for variations in practice patterns did not appreciably alter the results. When data were analyzed after only three or six months of treatment, the significant differences in treatment needs disappeared. CONCLUSIONS: The CHX chip is a new, apparently cost-effective treatment option for non-surgical periodontal therapy. Adjunctive use of the CHX chip could reduce periodontal surgical needs significantly at little or no additional cost. CLINICAL IMPLICATIONS: Results suggest that incorporating the CHX chip into routine practice requires a new algorithm for management of periodontal disease. To obtain full clinical benefit, treatment needs to be continued for nine months.

Trace elements in coal: environmental and health significance.

Trace elements can have profound adverse effects on the health of people burning coal in homes or living near coal deposits, coal mines, and coal-burning power plants. Trace elements such as arsenic emitted from coal-burning power plants in Europe and Asia have been shown to cause severe health problems. Perhaps the most widespread health problems are caused by domestic coal combustion in developing countries where millions of people suffer from fluorosis and thousands from arsenism. Better knowledge of coal quality characteristics may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals in coal may help to predict the behavior of the potentially toxic trace metals during coal cleaning, combustion, weathering, and leaching.

Health impacts of domestic coal use in China.

Domestic coal combustion has had profound adverse effects on the health of millions of people worldwide. In China alone several hundred million people commonly burn raw coal in unvented stoves that permeate their homes with high levels of toxic metals and organic compounds. At least 3,000 people in Guizhou Province in southwest China are suffering from severe arsenic poisoning. The primary source of the arsenic appears to be consumption of chili peppers dried over fires fueled with high-arsenic coal. Coal samples in the region were found to contain up to 35,000 ppm arsenic. Chili peppers dried over high-arsenic coal fires adsorb 500 ppm arsenic on average. More than 10 million people in Guizhou Province and surrounding areas suffer from dental and skeletal fluorosis. The excess fluorine is caused by eating corn dried over burning briquettes made from high-fluorine coals and high-fluorine clay binders. Polycyclic aromatic hydrocarbons formed during coal combustion are believed to cause or contribute to the high incidence of esophageal and lung cancers in parts of China. Domestic coal combustion also has caused selenium poisoning and possibly mercury poisoning. Better knowledge of coal quality parameters may help to reduce some of these health problems. For example, information on concentrations and distributions of potentially toxic elements in coal may help delineate areas of a coal deposit to be avoided. Information on the modes of occurrence of these elements and the textural relations of the minerals and macerals in coal may help predict the behavior of the potentially toxic components during coal combustion.

Local delivery of chemotherapeutic agents in periodontal therapy: has its time arrived?

The concept of locally delivering chemotherapeutic agents to the periodontal pocket as a method to treat periodontal disease has been studied for over 20 years. A number of locally delivered chemotherapeutic agents in periodontal therapy are either currently available or under investigation. Clinical efficacy derives from sustained-release technology to maintain an effective concentration of drug within the periodontal pocket for a clinically relevant length of time. Studied drugs have mainly been antimicrobials, both antibiotics and antiseptics. Most agents have been tested as adjuncts to scaling and root planing; a few have been studied as stand-alone monotherapies. Collectively, the data indicate that the use of locally delivered antimicrobials as adjuncts results in a significant increase in the reduction of probing depth compared with scaling and root planing alone. In other trials, results in reducing probing depth following the use of stand-alone locally delivered antimicrobials have been equivalent to those of scaling and root planing over a specified time. This Symposium was organized to present the current state-of-the-art with regard to the use of locally delivered antimicrobials in the treatment of periodontal disease. 5 experts in the field who have had considerable experience in studying locally delivered antimicrobials presented data. These speakers reviewed the clinical findings regarding efficacy of 5 different antimicrobial agents. An ensuing panel discussion was to consider treatment recommendations for locally delivered antimicrobials.

The etiology of Balkan endemic nephropathy: still more questions than answers.

Balkan endemic nephropathy (BEN) has attracted increasing attention as a possible environmental disease, and a significant amount of research from complementary scientific fields has been dedicated to its etiology. There are two actual competing theories attempting to explain the cause of this kidney disease: 1) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A ingested intermittently in small amounts by the individuals in the endemic regions, and 2) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low rank coals underlying or proximal to the endemic settlements. We outline the current developments and future prospects in the study of BEN and differentiate possible factors and cofactors in disease etiology.

Adjunctive use of a subgingival controlled-release chlorhexidine chip reduces probing depth and improves attachment level compared with scaling and root planing alone.

The present studies evaluated the efficacy of a controlled-release biodegradable chlorhexidine (CHX) (2.5 mg) chip when used as an adjunct to scaling and root planing on reducing probing depth (PD) and improving clinical attachment level (CAL) in adult periodontitis. Two double-blind, randomized, placebo-controlled multi-center clinical trials (5 centers each) were conducted; pooled data are reported from all 10 centers (447 patients). At baseline, following 1 hour of scaling and root planing (SRP) in patients free of supragingival calculus, the chip was placed in target sites with PD 5 to 8 mm which bled on probing. Chip placement was repeated at 3 and/or 6 months if PD remained > or = 5 mm. Study sites in active chip subjects received either CHX chip plus SRP or SRP alone (to maintain study blind). Sites in placebo chip subjects received either placebo chip plus SRP or SRP alone. Examinations were performed at baseline; 7 days; 6 weeks; and 3, 6, and 9 months. At 9 months significant reductions from baseline favoring the chlorhexidine chip compared with both control treatments were observed with respect to PD (chlorhexidine chip plus SRP, 0.95 +/- 0.05 mm; SRP alone, 0.65 +/- 0.05 mm, P < 0.001; placebo chip plus SRP, 0.69 +/- 0.05 mm, P < 0.001) and CAL (chlorhexidine chip plus SRP, 0.75 +/- 0.06 mm; SRP alone, 0.58 +/- 0.06 mm, P < 0.05; placebo chip plus SRP, 0.55 +/- 0.06 mm, P < 0.05). The proportion of patients who evidenced a PD reduction from baseline of 2 mm or more at 9 months was significantly greater in the chlorhexidine chip group (19%) compared with SRP controls (8%) (P < 0.05). Adverse effects were minor and transient toothache, including pain, tenderness, aching, throbbing, soreness, discomfort, or sensitivity was the only adverse effect that was higher in the chlorhexidine group as compared to placebo (P = 0.042). These data demonstrate that the adjunctive use of the chlorhexidine chip results in a significant reduction of PD when compared with both SRP alone or the adjunctive use of a placebo chip. These multi-center randomized control trials suggest that the chlorhexidine chip is a safe and effective adjunctive chemotherapy for the treatment of adult periodontitis.

Comparative effects of platelet-derived growth factor-BB and insulin-like growth factor-I, individually and in combination, on periodontal regeneration in Macaca fascicularis.

Platelet-derived growth factor (PDGF) and insulin-like growth factor I (IGF-I) in combination have previously been shown to enhance periodontal regeneration. The objective of this study was to further characterize the biological effects of this combination of growth factors in non-human primates and compare the effects to those of each growth factor individually. Ligature-induced periodontitis was initiated in 10 cynomolgus monkeys. After periodontal lesions were established, surgery was performed, and either a methylcellulose gel vehicle or vehicle containing 10 micrograms each of either PDGF-BB, IGF-I or both PDGF-BB and IGF-I was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after treatment and the extent of periodontal regeneration was assessed by histomorphometry. At both 4 and 12 wk vehicle-treated lesions generally revealed minimal osseous defect fill (ODF) (8.5 +/- 2.1% and 14.5 +/- 5.7%, respectively) and new attachment (NA) (34.1 +/- 5.2% and 26.6 +/- 10.5%, respectively). IGF-I treatment did not significantly alter healing compared to vehicle in any parameter at both 4 and 12 wk. PDGF-BB-treated sites exhibited significant (p < 0.05) regeneration of NA (69.6 + 12.0%) at 12 wk; trends for PDGF-BB treatment effect were also observed in other parameters at 4 and 12 wk, although these increases were not statistically significant. Treatment with PDGF-BB/IGF-I resulted in 21.6 +/- 5.1% and 42.5 +/- 8.3% ODF at 4 and 12 wk, respectively, and 64.1 +/- 7.7% and 74.6 +/- 7.4% NA at 4 and 12 wk, respectively (all significantly greater than vehicle, p < 0.05). The results from this study demonstrated that: 1) IGF-I alone at the dose tested did not significantly alter periodontal wound healing; 2) PDGF-BB alone significantly stimulated NA, with trends of effect on other parameters; and 3) the PDGF-BB/IGF-I combination resulted in significant increases in NA and ODF above vehicle at both 4 and 12 wk.

The effect of systemically administered PDGF-BB on the rodent skeleton.

Platelet-derived growth factor (PDGF), an osteoblast mitogen, has been demonstrated to accelerate fracture healing and periodontal bone repair when applied locally in vivo. To explore whether PDGF could stimulate bone formation in intact bone, we administered it systemically to rats rendered acutely estrogen-deficient. Because PDGF may stimulate bone resorption in vitro, PDGF was administered with and without an antiresorptive agent (alendronate). All treatments were given by intravenous injection 3 times a week for 6 weeks. Spinal bone mineral density (BMD) decreased by 5% in the vehicle-treated ovariectomized (OVX) rats by the end of the study as determined by DXA. Treatment with PDGF prevented this bone loss and significantly (p < 0.05) increased the bone density in the spine (9%) and whole skeleton (5.8%). Combined treatment with PDGF and alendronate resulted in a greater increase at the spine (18%) and whole skeleton (12.8%) than either agent alone. Histomorphometric analysis demonstrated that treatment with PDGF increased the osteoblast number and osteoblast perimeter without consistent changes in osteoclast estimates. Biomechanical testing demonstrated that PDGF administration increased the vertebral body compressive strength and femoral shaft torsional stiffness and resulted in a trend for enhanced femoral head shearing strength. Coadministration of alendronate further increased these indices of bone strength. PDGF administration also caused premature closure of the growth plate, decreased body fat, and resulted in extraskeletal collagen deposition. We therefore demonstrate, for the first time, that systemic administration of PDGF can increase bone density and strength throughout the skeleton.

An age-related decrease in the concentration of insulin-like growth factor binding protein-5 in human cortical bone.

The skeletal contents of insulin-like growth factor-2 (IGF-II), insulin-like growth factor binding protein-5 (IGFBP-5), and insulin-like growth factor binding protein-3 (IGFBP-3) were determined in duplicate samples of human femoral cortical bone obtained from 64 subjects (44 males and 20 females) between the ages of 20 and 64 years. The results of these quantitative measurements revealed an age-related decrease in the femoral cortical content of IGFBP-5 (r = -0.272, P = 0.031) in the total population. Although the femoral cortical content of IGF-II did not show a similar decrease with age, it could be correlated to the femoral cortical content of IGFBP-5 (r = 0.442, P < 0.001). In contrast, the femoral cortical content of IGFBP-3 did not decrease with age and could not be correlated to the femoral cortical contents of either IGFBP-5 or IGF-II. Comparisons of these results with previous measurements of insulin-like growth factor-1 (IGF-I) and transforming growth factor-beta (TGF-beta), in extracts of the same bones, showed significant cross-correlations between the femoral cortical contents of each of these growth factors and the femoral cortical contents of IGFBP-5 (r = 0.625 for IGF-I versus IGFBP-5, r = 0.554 for TGF-beta versus IGFBP-5, P < 0.001 for each) but not IGFBP-3.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of canine and non-human primate animal models for periodontal regenerative therapy: results following a single administration of PDGF/IGF-I.

Two commonly used animal models for evaluating putative periodontal regenerative therapies are the beagle dog model with natural periodontal disease and the non-human primate with ligature-induced attachment loss. The host response, microbiology, and skeletal rates of remodeling of these two models are summarized. In addition, the results of experiments comparing the healing response to periodontal surgery with and without concurrent use of the combination of platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) in these models are presented. At 1 month, PDGF/IGF-I administration resulted in a 64.1% and 51.4% increase in new attachment formation in the non-human primate and canine, respectively, while controls (surgery plus placebo) demonstrated 34.1% and 8.6% increases in new attachment formation in the non-human primate and canine models, respectively. Further, application of PDGF/IGF-I stimulated 21.6% and 65% osseous defect fill in the non-human primate and canine, respectively, while controls demonstrated 8.5% and 14.5% osseous defect fill in the non-human primate and canine, respectively. The osseous response in the canine appears greater than that of the non-human primate, and the new attachment formation was more substantial in the non-human primate than the canine. However, in general these data demonstrate a high degree of consistency in the effects of PDGF/IGF-I in promoting periodontal regeneration. Positive results in these two models--the dog with natural periodontal disease and the non-human primate with ligature-induced attachment loss--justify human clinical trial testing of a putative regenerative therapy.