The Role of BRAF Inhibitors in the Management of Ameloblastoma: A Literature Review.

Ameloblastoma is one of the most prevalent but enigmatic benign odontogenic tumors of the jaw, accounting for approximately 10% of all maxillary and mandibular tumors. This neoplasia is distinguished by exhibiting several clinical and histological variants along with several mutations that affect its behavior. The ameloblastoma treatment plan is determined by the tumor's size, anatomical location, histologic variant, and anatomical involvement. On chromosome 7, there is a proto-oncogene called BRAF. When BRAF is mutated, it becomes an oncogene and continuously produces proteins like MEK and ERK, members of mitogen-activated protein kinase (MAPK). In the signaling pathway, these proteins activate transcription factor inside the nucleus that helps in cell division and growth. Numerous neoplasms have been linked to more than 40 BRAF mutations. The most common one is BRAF proto-oncogene serine/threonine kinase (BRAF) V600E, whose treatment has been linked to a positive outcome. BRAF inhibitors like vemurafenib, dabrafenib, and sorafenib have shown excellent results, especially in metastatic ameloblastoma. BRAF, particularly in the case of metastatic ameloblastoma, inhibitors such as vemurafenib, dabrafenib, and sorafenib, has demonstrated outstanding results. Targeted therapies have been employed as adjuvant therapies to enhance cosmetic outcomes, even though no reports of serial cases demonstrate their effectiveness in ameloblastomas. In the treatment of ameloblastomas, the identification of BRAF V600E and additional mutations as the prime targeted therapies has proven to be a significant breakthrough where surgical treatment was contraindicated. In this article, we review the presence of BRAF V600E mutations, their inhibitors, and targeted therapies in ameloblastoma.

The Role of 5-Fluorouracil in Preventing Recurrence After Enucleation of Odontogenic Keratocyst: A Case Report.

The odontogenic keratocyst (OKC) is known for its high recurrence rate and disputed treatment modalities. In this report, we review the literature elucidating the efficacy of 5-fluorouracil (5-FU) topical application for recurrent OKC, and discuss the management of an OKC with 5-FU after enucleation and a 12-month follow-up. A 38-year-old female patient with an aggressive OKC in the right mandible underwent surgical curettage followed by topical application of 5-FU. Regular follow-up examinations for 12 months (radiological evaluation at three, six, and 12-month intervals) showed no signs of recurrence, with complete resolution of the cystic lesion and gradual bone regeneration. New bone formation was identified in the radiographic follow-up.  This case demonstrates the potential efficacy of topical 5-FU as a promising treatment modality for OKC, warranting further research and validation. A novel and successful therapy for OKC is the topical application of 5-FU. After enucleation, topical application of 5-FU efficiently treats OKC, leading to normal bone healing and regeneration without any adverse local or systemic effects.

Interplay of legacy irrigation and nitrogen fertilizer inputs to spatial variability of arsenic and uranium within the deep vadose zone.

The vadose zone is a reservoir for geogenic and anthropogenic contaminants. Nitrogen and water infiltration can affect biogeochemical processes in this zone, ultimately affecting groundwater quality. In this large-scale field study, we evaluated the input and occurrence of water and nitrogen species in the vadose zone of a public water supply wellhead protection (WHP) area (defined by a 50-year travel time to groundwater for public supply wells) and potential transport of nitrate, ammonium, arsenic, and uranium. Thirty-two deep cores were collected and grouped by irrigation practices: pivot (n = 20), gravity (n = 4) irrigated using groundwater, and non-irrigated (n = 8) sites. Beneath pivot-irrigated sites, sediment nitrate concentrations were significantly (p < 0.05) lower, while ammonium concentrations were significantly (p < 0.05) higher than under gravity sites. The spatial distribution of sediment arsenic and uranium was evaluated against estimated nitrogen and water loading beneath cropland. Irrigation practices were randomly distributed throughout the WHP area and presented a contrasting pattern of sediment arsenic and uranium occurrence. Sediment arsenic correlated with iron (r = 0.32, p < 0.05), uranium negatively correlated to sediment nitrate (r = -0.23, p < 0.05), and ammonium (r = -0.19 p < 0.05). This study reveals that irrigation water and nitrogen influx influence vadose zone geochemistry and mobilization of geogenic contaminants affecting groundwater quality beneath intensive agricultural systems.

Labile carbon and soil texture control nitrogen transformation in deep vadose zone.

Understanding transient nitrogen (N) storage and transformation in the deep vadose zone is critical for controlling groundwater contamination by nitrate. The occurrence of organic and inorganic forms of carbon (C) and nitrogen and their importance in the deep vadose zone is not well characterized due to difficulty in sampling and the limited number of studies. We sampled and characterized these pools beneath 27 croplands with different vadose zone thicknesses (6-45 m). We measured nitrate and ammonium in different depths for the 27 sites to evaluate inorganic N storage. We measured total Kjeldahl nitrogen (TKN), hot-water extractable organic carbon (EOC), soil organic carbon (SOC), and δ13C for two sites to understand the potential role of organic N and C pools in N transformations. Inorganic N stocks in the vadose zone were 21.7-1043.6 g m-2 across 27 sites; the thicker vadose zone significantly stored more inorganic N (p < 0.05). We observed significant reservoirs of TKN and SOC at depths, likely representing paleosols that may provide organic C and N to subsurface microbes. The occurrence of deep C and N needs to be addressed in future research on terrestrial C and N storage potential. The increase of ammonium and EOC and δ13C value in the proximity of these horizons is consistent with N mineralization. An increase of nitrate, concurrent with the sandy soil texture and the water-filled pore space (WFPS) of 78 %, suggests that deep vadose zone nitrification may be supported in vadose zones with organic-rich layers such as paleosol. A profile showing the decrease of nitrate concentrations, concurrent with the clay soil texture and the WFPS of 91 %, also suggests denitrification may be an important process. Our study shows that microbial N transformation may be possible even in deep vadose zone with co-occurrence of C and N sources and controlled by labile C availability and soil texture.

Importance of snowmelt on soil nitrate leaching to groundwater - A model study.

The movement of nitrate to surface water bodies during snow accumulation and melting has been extensively studied, but there are only limited studies on the influence of snow processes on nitrate leaching to groundwater. The present study investigated the impact of snow processes on nitrate leaching to groundwater based on a simulation modeling approach using HYDRUS-1D. HYDRUS-1D model has a temperature threshold-based snow model in addition to water, solute, and heat simulation components. The snow component in HYDRUS-1D was previously not applied to snow simulation studies since the method does not consider a detailed physical and process-based representation of snow accumulation and melting. In the present study, HYDRUS-1D was used to simulate snow accumulation and melting over 30 years for a location in Waverly, Lancaster County, Nebraska, USA. From the simulations, it was observed that the calibrated temperature threshold based snow module in HYDRUS-1D is effective in simulating snow accumulation and melting, as shown by the index of agreement and root mean squared error of 0.74 and 2.70 cm for calibration (15 years) and 0.88 and 2.70 cm for validation (15 years), respectively. The impact of snow melt on nitrate leaching was studied based on a study area with corn cultivation (Waverly, Nebraska, USA). A long-term (60 years) analysis was carried out for irrigated and non-irrigated agriculture with and without precipitation as snow. A higher nitrate leaching to groundwater was observed in the order of irrigated-with snow (54,038 kg/ha), irrigated-without snow (53,516 kg/ha), non-irrigated-with snow (7,431 kg/ha), and non-irrigated-without snow (7,090 kg/ha). This displays a 0.98% and 4.81% increase in nitrate leaching due to snow in irrigated and non-irrigated conditions, respectively. When extrapolated over the corn cultivated regions in Nebraska, this resulted in a difference of 1.2E+09 kg and 6.1E+08 kg of nitrate when considering snow in irrigated and non-irrigated areas over 60 years. This is the first study that has analyzed the long-term impact of snow on nitrate transport to groundwater based on a simulation modeling approach. The results show that snow accumulation and melting plays a vital role in the nitrate leaching into the groundwater and indicates the importance of considering snow components in similar studies.

Evaluation of dissolved and acid-leachable trace element concentrations in relation to practical water quality standards in the Syr Darya, Aral Sea Basin, South Kazakhstan.

The Syr Darya is one of the major rivers supplying the Aral Sea with freshwater. Soviet programs aimed at maximizing agricultural productivity in the Syr Darya basin increased diversion of water drastically affecting its water quality with significant consequences to its suitability for irrigation, fisheries and other uses. While water quality standards for trace elements are typically measured in the dissolved phase, there is evidence that adsorbed phases may also be relevant. Here we report potentially available heavy metals and metalloid concentrations in the Syr Darya water through the treatment of unfiltered waters samples with dilute nitric acid. Significant differences were found for most studied elements (Mann-Whitney U Test, p < 0.05) between their dissolved and acid-leachable concentrations. For Sr and Se in both sampling campaigns, no significant differences were found between their dissolved and acid-leachable concentrations, indicating their low geochemical reactivity. Dissolved V concentrations and acid-leachable Ni and Zn were found to exceed Kazakhstan Maximum Permissible Concentrations (MPC) values for the protection of fishery water quality. Our study evaluates the importance of considering regulatory issues of measuring trace metal concentrations to assess the water suitability for fisheries and irrigation.

Self-functionalization of soil-aged biochar surfaces increases nitrate retention.

Nutrient retention in biochar amended soil has yielded variable results, with poorly understood mechanisms. Identification of changes on biochar surfaces during in situ soil aging can provide mechanistic information on the role of biochar on nutrient retention. In the current greenhouse study, we analyzed changes of biochar surface characteristics from aging in two soils with different iron levels and amended with two types of manure under corn. On pristine biochar surfaces, we detected no iron species. In contrast, after soil aging (70 days), a self-functionalization of biochar surfaces with iron oxides was observed, which can be explained by soil redox cycles allowing reduced iron(II) to migrate on biochar surfaces followed by its re-oxidation. This self-functionalization is proposed as an underlying mechanism explaining the significantly (p < 0.01) increased nitrate retention by 29-180 % in biochar amended soil. Significant (p < 0.05) reductions in leachate phosphate (18-41 %) and dissolved organic carbon (8.8-55 %) were also observed after biochar surface functionalization. Our results indicate that redox-driven iron oxide formation on surfaces of biochar in the soil can be a critical process explaining the dynamic nature of nutrient retention observed in biochar amended soils. Identifying soil environmental conditions most beneficial for such surface functionalization, which has the potential to increase nutrient retention, is critical for implementing efficient biochar amendment strategies and for increased resource efficiency in agroecosystems.

Evaluating coal char as an alternative to biochar for mitigating nutrient and carbon loss from manure-amended soils: Insights from a greenhouse experiment.

Animal manure has been increasingly adopted as a more sustainable substitute for synthetic fertilizers but might result in increased dissolved organic C (DOC) and phosphate (PO4 3- ) leaching and elevated greenhouse gas emissions from soil. Biochar may reduce nutrient loss from manure-amended soils, but large-scale application has been hindered, in part, by its high cost. Minimum cost alternatives, such as incomplete coal combustion residue (char), may provide a more viable option to farmers, but char needs to be analyzed in comparison to high-temperature pine biochar before recommendations can be made. We valuated losses of soil C, N, and P, as well as plant yields and changes in microbial biomass, in two contrasting soils amended with dairy slurry or swine lagoon wastewater and with biochar or coal char over 105 d. Dissolved organic C leaching decreased with addition of biochar or char (0.6-27% or 1.6-36%), independent of soil texture and manure type. Leaching of PO4 3- was reduced by biochar (15-24%) and char (38-50%) in the silt loam. Soil N leaching increased after char application (likely due to our high application rate) but was unaffected by biochar. Char reduced CO2 emissions from the sandy loam by 9.7-54%, whereas both biochar and char increased CO2 emissions in the silt loam by 38-48% during plant root senescence. Depending on soil characteristics, char may outcompete biochar with respect to reduction of PO4 3- and DOC leaching. Unlike biochar, some char-N is available, and this should be accounted for when considering application rates.

Ferrihydrite enrichment in the rhizosphere of unsaturated soil improves nutrient retention while limiting arsenic and uranium plant uptake.

Improvement of nutrient use efficiency and limiting trace elements such as arsenic and uranium bioavailability is critical for sustainable agriculture and food safety. Arsenic and uranium possess different properties and mobility in soils, which complicates the effort to reduce their uptake by plants. Here, we postulate that unsaturated soil amended with ferrihydrite nanominerals leads to improved nutrient retention and helps reduce uptake of these geogenic contaminants. Unsaturated soil is primarily oxic and can provide a stable environment for ferrihydrite nanominerals. To demonstrate the utility of ferrihydrite soil amendment, maize was grown in an unsaturated agricultural soil that is known to contain geogenic arsenic and uranium. The soil was maintained at a gravimetric moisture content of 15.1 ± 2.5%, typical of periodically irrigated soils of the US Corn Belt. Synthetic 2-line ferrihydrite was used in low doses as a soil amendment at three levels (0.00% w/w (control), 0.05% w/w and 0.10% w/w). Further, the irrigation water was fortified (~50 µg L-1 each) with elevated arsenic and uranium levels. Plant dry biomass at maturity was ~13.5% higher than that grown in soil not receiving ferrihydrite, indicating positive impact of ferrihydrite on plant growth. Arsenic and uranium concentrations in maize crops (root, shoot and grain combined) were ~ 20% lower in amended soils than that in control soils. Our findings suggest that the addition of low doses of iron nanomineral soil amendment can positively influence rhizosphere geochemical processes, enhancing nutrient plant availability and reduce trace contaminants plant uptake in sprinkler irrigated agroecosystem, which is 55% of total irrigated area in the United States.

Source apportionment and health risk assessment of nitrate in foothill aquifers of Western Ghats, South India.

The present research reports the level of nitrate (NO3-), associated health risks and possible sources of contamination in groundwater from south India. Many samples (32%) are above or approaching the recommended level of NO3- for safe drinking water. The correlation analysis indicates different sources of NO3- contamination in different regions rather than a common origin. The isotopic measurements provide information about potential nitrogen sources contributing NO3- to the groundwater. Based on isotope analysis, the sources of NO3- in the groundwater of this region are likely to be from (a) septic sewage (b) organic nitrogen (animal and livestock excreta) (c) sewage (domestic & chemical fertilizers). Among the sample analyzed sewage, manure and septic sewage contribute 46%, 23% and 31% NO3- to groundwater. The HQ > 1 indicates non-carcinogenic health risk due to consumption of high NO3- in drinking water. Among the studied age groups, infants are exposed to higher risk than children and adults. Results indicate that groundwater of this region is polluted with NO3- due to anthropogenic activities. Continuous consumption of such water may pose serious health risk to the residents.

Occurrence of arsenite in surface and groundwater associated with a perennial stream located in Western Nebraska, USA.

Dissolved arsenic typically results from chemical weathering of arsenic rich sediments and is most often found in oxidized forms in surface water. The mobility of arsenic is controlled by its valence state and also by its association with iron oxides minerals, the forms of which are both influenced by abiotic and biotic processes in aqueous environment. In this study, speciation methods were used to measure and confirm the presence of reduced arsenic species in the surface water of Frenchman creek, a gaining stream that crosses the Colorado-Nebraska border. Selective extraction analysis of aquifer and stream bed sediments shows that the bulk of the arsenic occurs with labile iron-rich oxy(hydroxide) minerals. Total dissolved arsenic in surface and groundwater ranged from ~3-18 µg L-1, and reduced arsenic species comprise about 41% of the total dissolved arsenic (16.0 µg L-1) in Frenchman creek. Leachable arsenic in the aquifer sediment samples ranged up to 1553 µg kg-1, while samples from Frenchman creek bed sediments contained 4218 µg kg-1. Dynamic surface and groundwater interaction sustains arsenite in iron-rich surface headwaters, and the implied toxicity of reduced arsenic in this hydrogeological setting, which can be important in surface water environments around the globe.

Nanomaterials in the environment, human exposure pathway, and health effects: A review.

Nanomaterials (NMs), both natural and synthetic, are produced, transformed, and exported into our environment daily. Natural NMs annual flux to the environment is around 97% of the total and is significantly higher than synthetic NMs. However, synthetic NMs are considered to have a detrimental effect on the environment. The extensive usage of synthetic NMs in different fields, including chemical, engineering, electronics, and medicine, makes them susceptible to be discharged into the atmosphere, various water sources, soil, and landfill waste. As ever-larger quantities of NMs end up in our environment and start interacting with the biota, it is crucial to understand their behavior under various environmental conditions, their exposure pathway, and their health effects on human beings. This review paper comprises a large portion of the latest research on NMs and the environment. The article describes the natural and synthetic NMs, covering both incidental and engineered NMs and their behavior in the natural environment. The review includes a brief discussion on sampling strategies and various analytical tools to study NMs in complex environmental matrices. The interaction of NMs in natural environments and their pathway to human exposure has been summarized. The potential of NMs to impact human health has been elaborated. The nanotoxicological effect of NMs based on their inherent properties concerning to human health is also reviewed. The knowledge gaps and future research needs on NMs are reported. The findings in this paper will be a resource for researchers working on NMs all over the world to understand better the challenges associated with NMs in the natural environment and their human health effects.

Ferrihydrite Reduction Increases Arsenic and Uranium Bioavailability in Unsaturated Soil.

Redox driven mobilization and plant uptake of contaminants under transiently saturated soil conditions need to be clarified to ensure food and water quality across different irrigation systems. We postulate that solid-phase iron reduction in anoxic microsites present in the rhizosphere of unsaturated soil is a key driver for mobilization and bioavailability of contaminants under nonflooded irrigation. To clarify this, two major crops, corn and soybean differing in iron uptake strategies, were grown in irrigated synthetic soil under semiarid conditions with gravimetric moisture content ∼12.5 ± 2.4%. 2-line ferrihydrite, which was coprecipitated with uranium and arsenic, served as the only iron source in soil. Irrespective of crop type, reduced iron was detected in pore water and postexperiment rhizosphere soil confirming ferrihydrite reduction. These results support the presence of localized anoxic microsites in the otherwise aerobic porous bulk soil causing reduction of ferrihydrite and concomitant increase in plant uptake of comobilized contaminants. Our findings indicate that reactive iron minerals undergo reductive dissolution inside anoxic microsites of primarily unsaturated soil, which may have implications on the mobility of trace element contaminants such as arsenic and uranium in irrigated unsaturated soils, accounting for 55% of the irrigated area in the US.

Optimum rates of surface-applied coal char decreased soil ammonia volatilization loss.

Fertilizer N losses from agricultural systems have economic and environmental implications. Soil amendment with high C materials, such as coal char, may mitigate N losses. Char, a coal combustion residue, obtained from a sugar factory in Scottsbluff, NE, contained 29% C by weight. A 30-d laboratory study was conducted to evaluate the effects of char addition on N losses via nitrous oxide (N2 O) emission, ammonia (NH3 ) volatilization, and nitrate (NO3 -N) leaching from fertilized loam and sandy loam soils. Char was applied at five different rates (0, 6.7, 10.1, 13.4, and 26.8 Mg C ha-1 ; char measured in C equivalent) to soils fertilized with urea ammonium nitrate (UAN) at 200 kg N ha-1 . In addition, there were two negative-UAN control treatments: no char (no UAN) and char at 26.8 Mg C ha-1 (no UAN). Treatment applied at 6.7 and 10.1 Mg C ha-1 in fertilized sandy loam reduced NH3 volatilization by 26-37% and at 6.7, 10.1, and 13.4 Mg C ha-1 in fertilized loam soils by 24% compared with no char application. Nitrous oxide emissions and NO3 -N leaching losses were greater in fertilized compared with unfertilized soil, but there was no effect of char amendment on these losses. Because NO3 -N leaching loss was greater in sandy loam than in loam, soil residual N was twofold higher in loam than in sandy loam. This study suggests that adding coal char at optimal rates may reduce agricultural reactive N to the atmosphere by decreasing NH3 volatilization from fertilized soils.

Detection, occurrence, and fate of emerging contaminants in agricultural environments (2020).

A review of 79 papers published in 2019 is presented. The topics ranged from detailed descriptions of analytical methods, to fate and occurrence studies, to ecological effects and sampling techniques for a wide variety of emerging contaminants likely to occur in agricultural environments. New methods and studies on veterinary pharmaceuticals, antibiotics, anthelmintics, and engineered nanomaterials in agricultural environments continue to expand our knowledge base on the occurrence and potential impacts of these compounds. This review is divided into the following sections: Introduction, Analytical Methods, Antibiotics in Agroecosystems, Pharmaceutical Fate and Occurrence, Anthelmintics and Engineered Nanomaterials. PRACTITIONER POINTS: New research describes innovative new techniques for emerging contaminant detection in agricultural settings Newer classes of contaminants include human and veterinary pharmaceuticals Research in nanomaterials show that these also occur in agricultural environments and will likely be topics of future work.

Detection, occurrence, and fate of emerging contaminants in agricultural environments (2019).

A review of 82 papers published in 2018 is presented. The topics ranged from detailed descriptions of analytical methods, to fate and occurrence studies, to ecological effects and sampling techniques for a wide variety of emerging contaminants likely to occur in agricultural environments. New methods and studies on veterinary pharmaceuticals, microplastics, and engineered nanomaterials in agricultural environments continue to expand our knowledge base on the occurrence and potential impacts of these compounds. This review is divided into the following sections: Introduction, Analytical Methods, Fate and Occurrence, Pharmaceutical Metabolites, Anthelmintics, Microplastics, and Engineered Nanomaterials. PRACTITIONER POINTS: New research describes innovative new techniques for emerging contaminant detection in agricultural settings. Newer classes of contaminants include human and veterinary pharmaceuticals. Research in microplastics and nanomaterials shows that these also occur in agricultural environments and will likely be topics of future work.

Rapid decadal evolution in the groundwater arsenic content of Kolkata, India and its correlation with the practices of her dwellers.

Increasing arsenic contamination in the groundwater is one of the biggest environmental challenges that the Bengal delta is facing today. Groundwater is still the main source of water for a large number of population in this region and therefore, significant presence of toxic arsenic has a direct consequence on human lives here. Moreover, arsenic also enters into the food chain through the consumed agricultural products grown in this area. Therefore, acquiring knowledge about the ever-changing map of arsenic contamination and employing adequate protective measures are of utmost importance. Here, we present a comprehensive municipal ward-wise map of the arsenic content of the shallow groundwater table of Kolkata-the most important and highly population dense city of the delta. Comparison with previously available data reveals a rapid change and the grim situation for the city. Our study suggests that it should be an immediate task of the administration to extend treated water service to the whole population of the city for direct consumption, and artificial recharge and maximum rainwater replenishment need to be taken up with utmost urgency to avoid intrusion of toxicity in biological food chains via agricultural products. We hope our study would drive the city planners to reconsider the existing urbanization and development plans of all the cities, placed over arsenic-contaminated groundwater aquifers.

Efficient artificial mineralization route to decontaminate Arsenic(III) polluted water - the Tooeleite Way.

Increasing exposure to arsenic (As) contaminated ground water is a great threat to humanity. Suitable technology for As immobilization and removal from water, especially for As(III) than As(V), is not available yet. However, it is known that As(III) is more toxic than As(V) and most groundwater aquifers, particularly the Gangetic basin in India, is alarmingly contaminated with it. In search of a viable solution here, we took a cue from the natural mineralization of Tooeleite, a mineral containing Fe(III) and As(III)ions, grown under acidic condition, in presence of SO4(2-) ions. Complying to this natural process, we could grow and separate Tooeleite-like templates from Fe(III) and As(III) containing water at overall circumneutral pH and in absence of SO4(2-) ions by using highly polar Zn-only ends of wurtzite ZnS nanorods as insoluble nano-acidic-surfaces. The central idea here is to exploit these insoluble nano-acidic-surfaces (called as INAS in the manuscript) as nucleation centres for Tooeleite growth while keeping the overall pH of the aqueous media neutral. Therefore, we propose a novel method of artificial mineralization of As(III) by mimicking a natural process at nanoscale.