Advances in In Vitro Blood-Air Barrier Models and the Use of Nanoparticles in COVID-19 Research.

Respiratory infections caused by coronaviruses (CoVs) have become a major public health concern in the past two decades as revealed by the emergence of SARS-CoV in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019. The most severe clinical phenotypes commonly arise from exacerbation of immune response following the infection of alveolar epithelial cells localized at the pulmonary blood-air barrier. Preclinical rodent models do not adequately represent the essential genetic properties of the barrier, thus necessitating the use of humanized transgenic models. However, existing monolayer cell culture models have so far been unable to mimic the complex lung microenvironment. In this respect, air-liquid interface models, tissue engineered models, and organ-on-a-chip systems, which aim to better imitate the infection site microenvironment and microphysiology, are being developed to replace the commonly used monolayer cell culture models, and their use is becoming more widespread every day. On the contrary, studies on the development of nanoparticles (NPs) that mimic respiratory viruses, and those NPs used in therapy are progressing rapidly. The first part of this review describes in vitro models that mimic the blood-air barrier, the tissue interface that plays a central role in COVID-19 progression. In the second part of the review, NPs mimicking the virus and/or designed to carry therapeutic agents are explained and exemplified.

Development of a Tri-Layered Vascular Construct and In Vitro Evaluation of Endothelization.

Advances in the development of vascular substitutes for small-sized arteries are ongoing because the present grafts do not entirely meet the requirements of native equivalents and are suboptimal in clinical performance. This study aims to develop a tri-layered vascular construct mimicking natural tissue using polyester blends and to investigate its endothelization through in vitro studies as a potential small-caliber vascular graft. The innermost layer is obtained by dip coating as a tubular porous film with a lumen diameter of 3 mm and a pore size of ≤8 µm. Circumferentially aligned electrospun fiber (diameter 100-800 nm) with a deviation angle of 15° are deposited over the porous film forming the intermediate layer. The random electrospun fibers (diameter 100-1100 nm) deviating at different angles are wrapped as the outermost layer. The mechanical properties of the tri-layered vascular construct are determined to be 44.80 ± 14.80 MPa for Young's modulus and 4.25 ± 0.75 MPa for ultimate tensile strength. MTS and cell behavior studies show that the isolated human umbilical cord vein endothelial cells proliferate and line the lumen of the vascular substitute. The vascular construct developed, with its biomimetic architecture, mechanical features, size, and endothelization, can be tested with in vivo studies.

Workplace flexibility, work-family interface, and psychological distress: differences by family caregiving obligations and gender.

Drawing on data from the 2008 U.S. National Study of the Changing Workforce, this study (1) examines the associations between access to three types of flexible working arrangements-flextime, flexplace, and culture of flexibility-and psychological distress, (2) tests the mediating roles of work-family conflict and work-family enrichment, and (3) investigates whether these relationships differ by workers' childcare or elder-care obligations as they intersect with gender. Results show that a flexible workplace culture, but not access to flextime or flexplace, is associated with lower psychological distress. Work-family conflict and work-family enrichment partially mediate the relationship between culture of flexibility and psychological distress. In addition, the negative effect of culture of flexibility on psychological distress is stronger among workers sandwiched between preschool childcare and elder-care compared with those with neither caregiving obligations, a pattern especially pronounced among women. We discuss these results and their implications for organizational practices and worker well-being.

UAV-based RGB and TIR imaging for geothermal monitoring: a case study at Kestanbol geothermal field, Northwestern Turkey.

Kestanbol is one of the most important geothermal fields in NW Turkey. This study conducted the first-ever surveys over a 10 ha reach of the Kestanbol geothermal field using an unmanned aerial vehicle (UAV) equipped with visible (RGB) and thermal infrared (TIR) cameras. Low-altitude flights below 40 m above the ground were operated above the Kestanbol geothermal field. Approximately 3500 RGB and TIR images were captured using the UAV. We recorded high-resolution RGB and TIR data of the Kestanbol geothermal field and applied the structure from motion (SfM) algorithm to identify the distribution of geothermal springs and seeps. The Kestanbol geothermal field was monitored to create a georeferenced RGB orthophoto, RGB 3D surface model, thermal anomaly map, and digital surface model (DSM) of the area with centimeter-level accuracy. In the TIR orthophoto, the surface temperature in the geothermal field was found to be between 15 and 75 °C. All the thermal anomalies revealed by the survey were verified by field observations. The geothermal springs and seeps were parallel to the NE-SW regional tectonic trends. The results of this study demonstrate an effective technique for monitoring and assessing geothermal water using UAV-based RGB and TIR imaging and provide an accurate basis for geothermal development projects. RGB and TIR imaging using UAVs are considered promising methods for improving the assessment of the effects of geothermal water on the environment.

Metronidazole induced cerebellar toxicity after prolonged treatment of large multiloculated pyogenic liver abscess; A case report and literature review.

Metronidazole is a common antibiotic agent for hepatic abscesses, which require both gram-negative and anaerobic coverage. Rarely, this antibiotic has been found to induce encephalopathy. Here, we describe a 65-year-old male who was treated with metronidazole for his hepatic abscess, who presented with syncope and questionable seizure and was found to have magnetic resonance imaging (MRI) brain findings consistent with metronidazole toxicity. Our patient demonstrated striking brain MRI findings which can be used to further understand the process behind this medication-induced toxicity. Hypotheses of this mechanism include swelling of axons secondary to increased water or vasospasm leading to reversible ischemia that is localized in the brain. In terms of MRI findings, brain lesions tend to populate bilaterally with focus at the dorsal pons, midbrain, cerebellar dentate nuclei (as with our patient), dorsal medulla, or splenium of corpus callosum. Additional research is warranted regarding this rare manifestation and timely removal of the offending agent is crucial for reversal of symptoms.

A Rare Case of Paraneoplastic Syndrome of Inappropriate Secretion of Antidiuretic Hormone in Cervical Squamous Cell Carcinoma; A Case Report and Literature Review.

SIADH is more commonly associated with small cell lung cancer but has also been associated with other malignancies such as oropharyngeal, gastrointestinal, genitourinary, endocrine, lymphomas, and sarcomas. There have been few reports of small cell carcinoma of the cervix complicated by SIADH; however, not many cases are associated with squamous cell carcinoma of the cervix. We present a case of a patient with squamous cell carcinoma of the cervix with a paraneoplastic syndrome of inappropriate secretion of antidiuretic hormone. The pathophysiology, clinical picture, and treatment are also discussed.

Work-family conflict and depressive symptoms among dual-earner couples in Germany: A dyadic and longitudinal analysis.

This study contributes to the existing literature by testing the longitudinal effects of both types of work-family conflict (i.e., work-to-family conflict [WTFC] and family-to-work conflict [FTWC]) on depressive symptoms, using data from three waves of the German Family Panel (pairfam) survey collected over a four-year period. Using responses from 631 married or cohabiting heterosexual couples, the analyses are estimated using dyadic data analysis and auto-regressive and cross-lagged panel models. This analytical approach tests direct causation, reverse causation, and reciprocal relationships among WTFC, FTWC and depressive symptoms. The results suggest a reciprocal relationship with significant cross-lagged actor effects between WTFC (and FTWC) and depressive symptoms. However, there were no gender differences in the cross-lagged actor effects between men and women, and no significant partner effects. These results highlight the bidirectional nature of the relationship between work-family conflict and depressive symptoms, which has several implications for research and practice.

Fabrication of a 3D Printed PCL Nerve Guide: In Vitro and In Vivo Testing.

Nerve guides are medical devices designed to guide proximal and distal ends of injured peripheral nerves in order to assist regeneration of the damaged nerves. A 3D-printed polycaprolactone (PCL) nerve guide using an aligned gelatin-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) electrospun mat, seeded with PC12 and Schwann cells (SCs) is produced. During characterization with microCT and SEM porosity (55%), pore sizes (675 ± 40 µm), and fiber diameters (382 ± 25 µm) are determined. Electrospun fibers have degree of alignment of 7°, indicating high potential for guidance. On Day 14, PC12 cells migrated from proximal to distal end of nerve guide when SCs are seeded on the guide. After 28 days, over 95% of PC12 are alive and aligned. PC12 cells express early differentiation marker beta-tubulin 10 times more than late marker NeuN. In a 10 mm rat sciatic nerve injury, functional recovery evaluated by using static sciatic index (SSI) is observed in mat-free guides and guides containing mat and SCs. Nerve conduction velocities are also improved in these groups. Histological stainings showed tissue growth around nerve guides with highest new tissue organization being observed with mat and cell-free guides. These suggest 3D-printed PCL nerve guides have significant potential for treatment of peripheral nerve injuries.

CD4+ and CD25+ T-cell response to short-time interferon-beta therapy on IL10, IL23A and FOXP3 genes in multiple sclerosis patients.

AIM OF THE STUDY: Interferon-beta (IFN-ß), multiple sclerosis (MS) drug for years, does not have therapeutic effects on each patient. Yet, a considerable portion has experienced no therapeutic response to IFN-ß. Therefore, it is necessary to determine disease-specific biomarkers that affect drug response. Here, we aimed to determine the effects of interleukin 10 (IL10) and 23 (IL23A), as well as forkhead box P3 (FOXP3) genes on MS after IFN-ß therapy. MATERIALS AND METHODS: Peripheral blood mononuclear cells (PBMCs) of 42 MS patients were isolated to obtain CD4+ and CD25+ T cells. Both cell types were characterised by flow cytometry. To determine optimum drug concentration of IFN-ß, cytotoxicity assays were assessed on each cell type for 4, 16, 24 and 48 hours respectively. Then, cells were cultured in the presence of 500 IU/mL of IFN-ß. cDNA synthesis was performed after mRNA extraction. RT-PCR was performed to measure gene expressions of IL10, IL23A and FOXP3. Results were evaluated statistically. RESULTS: It was found that the cytotoxic effect of IFN-ß was more efficient as the exposure time was expanded regardless of drug concentration. Moreover, CD25+ T lymphocytes were more resistant to IFN-ß. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48 hours in CD4+ T cells. For CD25+ T cells, the graded increase in FOXP3 was obtained while IL10 expression was gradually decreased throughout the drug intake. CONCLUSION: Although a considerable change in expression was obtained, the long-term IFN-ß effect on both genes and cells should be determined by follow-up at least a year.

An in vitro 3D diabetic human skin model from diabetic primary cells.

Diabetes mellitus, a complex metabolic disorder, leads to many health complications like kidney failure, diabetic heart disease, stroke, and foot ulcers. Treatment approaches of diabetes and identification of the mechanisms underlying diabetic complications of the skin have gained importance due to continued rapid increase in the diabetes incidence. A thick and pre-vascularized in vitro 3D type 2 diabetic human skin model (DHSM) was developed in this study. The methacrylated gelatin (GelMA) hydrogel was produced by photocrosslinking and its pore size (54.85 ± 8.58 µm), compressive modulus (4.53 ± 0.67 kPa) and swelling ratio (17.5 ± 2.2%) were found to be suitable for skin tissue engineering. 8% GelMA hydrogel effectively supported the viability, spreading and proliferation of human dermal fibroblasts. By isolating dermal fibroblasts, human umbilical vein endothelial cells and keratinocytes from type 2 diabetic patients, an in vitro 3D type 2 DHSM, 12 mm in width and 1.86 mm thick, was constructed. The skin model consisted of a continuous basal epidermal layer and a dermal layer with blood capillary-like structures, ideal for evaluating the effects of anti-diabetic drugs and wound healing materials and factors. The functionality of the DHSM was showed by applying a therapeutic hydrogel into its central wound; especially fibroblast migration to the wound site was evident in 9 d. We have demonstrated that DHSM is a biologically relevant model with sensitivity and predictability in evaluating the diabetic wound healing potential of a therapeutic material.

Metal removal from acid mine lake using ultrasound-assisted modified fly ash at different frequencies.

Acid mine drainage/lakes (AMD/AMLs) have a low pH with high concentrations of metals and sulfate and have been a major environmental problem in the Can Coal Basin, in northwestern Turkey. In this study, metal removal from Hayirtepe AML by using fly ash (FA) and modified fly ash (MFA) was investigated in batch experiments. The effects of various parameters, such as ultrasonic frequency, dose, contact time, pH, and temperature, were examined to determine the optimum conditions for metal removal from AML. This study also focused on the application of ultrasound-assisted modification by using a 20-kHz ultrasonic probe and a 40-kHz ultrasonic bath to increase the FA surface and improve its adsorption capacity for metal removal. FA modification at 20 kHz showed better results than that at 40 kHz because it produced rapid bubble implosion with acoustic cavitation. The FA and MFAs selectivity for metal removal was 98%-99% for Fe, 96%-99% for Al, 94%-97% for Zn, 90%-95% for Co, 88%-94% for Ni, 77%-92% for Cu, and 74%-92% for Mn according to the determined optimum parameters. Scanning electron microscopy coupled with the energy-dispersive X-ray spectroscopy (SEM/EDX) and X-ray diffractometry of the solid residues (SRs) identified gypsum as a new mineral phase from sulfate removal from the AML. Inductively coupled plasma mass spectrometry and SEM/EDX analysis revealed that the metal content of the SRs increased. The adsorption process fitted the pseudo-second order kinetic model. Thermodynamic parameters showed that the process was exothermic and the randomness of the solid/solution interface increased during adsorption. Reuse experiments indicated that the MFAs were reused more effectively for metal removal from AML compared with the FA. This study showed that the use of MFAs with a high adsorption capacity and surface area is economic and efficient for metal removal from AML.

Work-Family Conflict and Well-Being among German Couples: A Longitudinal and Dyadic Approach.

This study examines dual-earner couples to determine whether changes in work-family conflict predict changes in one's own (i.e., actor effects) or partner's (i.e., partner effects) health and well-being as well as gender differences in these relationships. Using data from 1,001 dual-earner couples in Wave 6 and Wave 8 of the German Family Panel survey (Pairfam), we found (1) significant actor effects for all outcomes, with stronger actor effects among men than women on mental health; (2) significant partner effects for life satisfaction and mental health, with stronger partner effects among men than women on life satisfaction; and (3) stronger actor effects than corresponding partner effects for life satisfaction and mental health. As work-family conflict has become a fact of life for many contemporary workers, our results contribute by highlighting the importance of using couple-level data and testing longitudinal crossover effects to provide a fuller understanding of such conflict's health consequences.

3D and 4D Printing of Polymers for Tissue Engineering Applications.

Three-dimensional (3D) and Four-dimensional (4D) printing emerged as the next generation of fabrication techniques, spanning across various research areas, such as engineering, chemistry, biology, computer science, and materials science. Three-dimensional printing enables the fabrication of complex forms with high precision, through a layer-by-layer addition of different materials. Use of intelligent materials which change shape or color, produce an electrical current, become bioactive, or perform an intended function in response to an external stimulus, paves the way for the production of dynamic 3D structures, which is now called 4D printing. 3D and 4D printing techniques have great potential in the production of scaffolds to be applied in tissue engineering, especially in constructing patient specific scaffolds. Furthermore, physical and chemical guidance cues can be printed with these methods to improve the extent and rate of targeted tissue regeneration. This review presents a comprehensive survey of 3D and 4D printing methods, and the advantage of their use in tissue regeneration over other scaffold production approaches.

A novel GelMA-pHEMA hydrogel nerve guide for the treatment of peripheral nerve damages.

Damage to the nervous system due to age, diseases or trauma may inhibit signal transfer along the nervous system. Nerve guides are used to treat these injuries by bridging the proximal and the distal end together. The design of the guide is very important for the reconnection of the severed axons. Methacrylated gelatin-poly(2-hydroxyethylmethacrylate) (GelMA-pHEMA) hydrogel was produced as the outer part of the nerve guide. pHEMA was added in various amounts into GelMA and increased the mechanical strength which is needed for the suturability of the guide. Porosity (15-70%), pore size (10-35 µm), water content (42-92%), and mechanical strength (65-710 kPa) of GelMA-pHEMA hydrogels were found to be suitable for nerve tissue engineering applications. Schwann cells attached and proliferated on GelMA, GelMA-pHEMA (5:5), and pHEMA hydrogels. Providing guidance is very important in the development of a nerve guide due to the anisotropic nature of the nerve tissue. Therefore, gelatin-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) aligned fiber mats were used inside of the nerve guide. High degree of alignment with low deviation (7°) of this mats provided PC12 cell alignment throughout the fibers. Combination of GelMA-pHEMA (5:5) hydrogel and gelatin-PHBV aligned mat would provide an ideal nerve guide for the treatment of peripheral nerve damages.

3D printed poly(ε-caprolactone) scaffolds modified with hydroxyapatite and poly(propylene fumarate) and their effects on the healing of rabbit femur defects.

A large variety of approaches have been used to treat large and irregular shaped bone defects with less than optimal success due to material or design issues. In recent years patient specific constructs prepared by additive manufacturing provided a solution to the need for shaping implants to fit irregular defects in the surgery theater. In this study, cylindrical disks of poly(ε-caprolactone) (PCL) were printed by fused deposition modeling and modified with nanohydroxyapatite (HAp) and poly(propylene fumarate) (PPF) to create a mechanically strong implant with well-defined pore size and porosity, controllable surface hydrophilicity (with PPF) and osteoconductivity (with HAp). Cytotoxicity, irritation and inflammation tests demonstrated that the scaffolds were biocompatible. PCL/HAp and PCL/HAp/PPF scaffolds were implanted in the femurs of rabbits with and without seeding with rabbit Bone Marrow Stem Cells (BMSC) and examined after 4 and 8 weeks with micro-CT, mechanically and histologically. BMSC seeded PCL/HAp/PPF scaffolds showed improved tissue regeneration as determined by bone mineral density and micro-CT. Compressive and tension stiffness values (394 and 463 N mm-1) were significantly higher than those of the healthy rabbit femur (316 and 392 N mm-1, respectively) after 8 weeks of implantation. These 3D implants have great potential for patient-specific bone defect treatments.

Prediction of acid mine drainage generation potential of various lithologies using static tests: Etili coal mine (NW Turkey) as a case study.

The Etili neighborhood in Can County (northwestern Turkey) has large reserves of coal and has been the site of many small- to medium-scale mining operations since the 1980s. Some of these have ceased working while others continue to operate. Once activities cease, the mining facilities and fields are usually abandoned without rehabilitation. The most significant environmental problem is acid mine drainage (AMD). This study was carried out to determine the acid generation potential of various lithological units in the Etili coal mine using static test methods. Seventeen samples were selected from areas with high acidic water concentrations: from different alteration zones belonging to volcanic rocks, from sedimentary rocks, and from coals and mine wastes. Static tests (paste pH, standard acid-base accounting, and net acid generation tests) were performed on these samples. The consistency of the static test results showed that oxidation of sulfide minerals, especially pyrite-which is widely found not only in the alteration zones of volcanic rocks but also in the coals and mine wastes-is the main factor controlling the generation of AMD in this mine. Lack of carbonate minerals in the region also increases the occurrence of AMD.

Generation of Acid Mine Lakes Associated with Abandoned Coal Mines in Northwest Turkey.

A total of five acid mine lakes (AMLs) located in northwest Turkey were investigated using combined isotope, molecular, and geochemical techniques to identify geochemical processes controlling and promoting acid formation. All of the investigated lakes showed typical characteristics of an AML with low pH (2.59-3.79) and high electrical conductivity values (1040-6430 µS/cm), in addition to high sulfate (594-5370 mg/l) and metal (aluminum [Al], iron [Fe], manganese [Mn], nickel [Ni], and zinc [Zn]) concentrations. Geochemical and isotope results showed that the acid-generation mechanism and source of sulfate in the lakes can change and depends on the age of the lakes. In the relatively older lakes (AMLs 1 through 3), biogeochemical Fe cycles seem to be the dominant process controlling metal concentration and pH of the water unlike in the younger lakes (AMLs 4 and 5). Bacterial species determined in an older lake (AML 2) indicate that biological oxidation and reduction of Fe and S are the dominant processes in the lakes. Furthermore, O and S isotopes of sulfate indicate that sulfate in the older mine lakes may be a product of much more complex oxidation/dissolution reactions. However, the major source of sulfate in the younger mine lakes is in situ pyrite oxidation catalyzed by Fe(III) produced by way of oxidation of Fe(II). Consistent with this, insignificant fractionation between δ(34) [Formula: see text] and δ(34) [Formula: see text] values indicated that the oxidation of pyrite, along with dissolution and precipitation reactions of Fe(III) minerals, is the main reason for acid formation in the region. Overall, the results showed that acid generation during early stage formation of an AML associated with pyrite-rich mine waste is primarily controlled by the oxidation of pyrite with Fe cycles becoming the dominant processes regulating pH and metal cycles in the later stages of mine lake development.

Laparoscopic anterior resection: new anastomosis technique in a pig model.

BACKGROUND AND OBJECTIVES: Bowel anastomosis after anterior resection is one of the most difficult tasks to perform during laparoscopic colorectal surgery. This study aims to evaluate a new feasible and safe intracorporeal anastomosis technique after laparoscopic left-sided colon or rectum resection in a pig model. METHODS: The technique was evaluated in 5 pigs. The OrVil device (Covidien, Mansfield, Massachusetts) was inserted into the anus and advanced proximally to the rectum. A 0.5-cm incision was made in the sigmoid colon, and the 2 sutures attached to its delivery tube were cut. After the delivery tube was evacuated through the anus, the tip of the anvil was removed through the perforation. The sigmoid colon was transected just distal to the perforation with an endoscopic linear stapler. The rectosigmoid segment to be resected was removed through the anus with a grasper, and distal transection was performed. A 25-mm circular stapler was inserted and combined with the anvil, and end-to-side intracorporeal anastomosis was then performed. RESULTS: We performed the technique in 5 pigs. Anastomosis required an average of 12 minutes. We observed that the proximal and distal donuts were completely removed in all pigs. No anastomotic air leakage was observed in any of the animals. CONCLUSION: This study shows the efficacy and safety of intracorporeal anastomosis with the OrVil device after laparoscopic anterior resection.

Collagen scaffolds with in situ-grown calcium phosphate for osteogenic differentiation of Wharton's jelly and menstrual blood stem cells.

The aim of this research was to investigate the osteogenic differentiation potential of non-invasively obtained human stem cells on collagen nanocomposite scaffolds with in situ-grown calcium phosphate crystals. The foams had 70% porosity and pore sizes varying in the range 50-200 µm. The elastic modulus and compressive strength of the calcium phosphate containing collagen scaffolds were determined to be 234.5 kPa and 127.1 kPa, respectively, prior to in vitro studies. Mesenchymal stem cells (MSCs) obtained from Wharton's jelly and menstrual blood were seeded on the collagen scaffolds and proliferation and osteogenic differentiation capacities of these cells from two different sources were compared. The cells on the composite scaffold showed the highest alkaline phosphatase activity compared to the controls, cells on tissue culture polystyrene and cells on collagen scaffolds without in situ-formed calcium phosphate. MSCs isolated from both Wharton's jelly and menstrual blood showed a significant level of osteogenic activity, but those from Wharton's jelly performed better. In this study it was shown that collagen nanocomposite scaffolds seeded with cells obtained non-invasively from human tissues could represent a potential construct to be used in bone tissue engineering.

Geochemical characterization of acid mine lakes in northwest Turkey and their effect on the environment.

Mining activity generates a large quantity of mine waste. The potential hazard of mine waste depends on the host mineral. The tendency of mine waste to produce acid mine drainage (AMD) containing potentially toxic metals depends on the amounts of sulfide, carbonate minerals, and trace-element concentrations found in ore deposits. The acid mine process is one of the most significant environmental challenges and a major source of water pollution worldwide. AMD and its effects were studied in northwest Turkey where there are several sedimentary and hydrothermal mineral deposits that have been economically extracted. The study area is located in Can county of Canakkale province. Canakkale contains marine, lagoon, and lake sediments precipitated with volcanoclastics that occurred as a result of volcanism, which was active during various periods from the Upper Eocene to Plio-Quaternary. Can county is rich in coal with a total lignite reserve >100 million tons and contains numerous mines that were operated by private companies and later abandoned without any remediation. As a result, human intervention in the natural structure and topography has resulted in large open pits and deterioration in these areas. Abandoned open pit mines typically fill with water from runoff and groundwater discharge, producing artificial lakes. Acid drainage waters from these mines have resulted in the degradation of surface-water quality around Can County. The average pH and electrical conductivity of acid mine lakes (AMLs) in this study were found to be 3.03 and 3831.33 µS cm(-1), respectively. Total iron (Fe) and aluminum (Al) levels were also found to be high (329.77 and 360.67 mg L(-1), respectively). The results show that the concentration of most elements, such as Fe and Al in particular, exceed national and international water-quality standards.