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Water has always been held in high respect by the Apsaálooke (Crow) people of Montana. Tribal members questioned the health of the rivers and well water because of visible water quality deterioration and potential connections to illnesses in the community. Community members initiated collaboration among local organizations, the tribe, and academic partners, resulting in genuine community-based participatory research. The article shares what we have learned as tribal members and researchers about working together to examine surface and groundwater contaminants, assess routes of exposure, and use our data to bring about improved health of our people and our waters. [ABSTRACT FROM AUTHOR]

Since the outbreak of the COVID-19 pandemic, races across academia and industry have been initiated to identify and develop disease modifying or preventative therapeutic strategies has been initiated. The primary focus has been on pharmacological treatment of the immune and respiratory system and the development of a vaccine. The hyperinflammatory state ("cytokine storm") observed in many cases of COVID-19 indicates a prognostically negative disease progression that may lead to respiratory distress, multiple organ failure, shock, and death. Many critically ill patients continue to be at risk for significant, long-lasting morbidity or mortality. The human immune and respiratory systems are heavily regulated by the central nervous system, and intervention in the signaling of these neural pathways may permit targeted therapeutic control of excessive inflammation and pulmonary bronchoconstriction. Several technologies, both invasive and non-invasive, are available and approved for clinical use, but have not been extensively studied in treatment of the cytokine storm in COVID-19 patients. This manuscript provides an overview of the role of the nervous system in inflammation and respiration, the current understanding of neuromodulatory techniques from preclinical and clinical studies and provides a rationale for testing non-invasive neuromodulation to modulate acute systemic inflammation and respiratory dysfunction caused by SARS-CoV-2 and potentially other pathogens. The authors of this manuscript have co-founded the International Consortium on Neuromodulation for COVID-19 to advocate for and support studies of these technologies in the current coronavirus pandemic., Competing Interests: CC is an equity holder of Convergent Medical Technologies, Inc., reports personal fees from electroCore Inc., and Spark Biomedical, and has issued and pending patents related to vagus nerve stimulation to control bleeding and inflammation. MB reports personal fees from Soterix Medical, grants from Google X, personal fees from Halo Neuroscience, outside the submitted work; in addition, he has a patent Brain Stimulation issued. MFr reports pending patent applications describing injectable electrode structures for Neuronoff, Inc., and is an employee and equity holder of Neuronoff, Inc. He further reports issued patents for selective Vagus nerve stimulation and selective electrical vagal block for regulation of autonomic functions such as heart rate and blood pressure for Boston Scientific. MFu reports personal fees from Axon Therapies, CVRx, Daxor, Edwards Life Sciences, Galvani, and Respicardia, outside the submitted work. SH is an employee and equity holder of Cala Health. NK reports a patent devices and methods for reducing inflammation using electrical stimulation pending. BS reports personal fees from electroCore, and reports patents issued and pending related to transcutaneous cervical vagus nerve stimulation. PS is an employee and equity holder of electroCore, and reports patents issued and pending related to transcutaneous cervical vagus nerve stimulation. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Czura, Bikson, Charvet, Chen, Franke, Fudim, Grigsby, Hamner, Huston, Khodaparast, Krames, Simon, Staats and Vonck.)

In-depth studies of the microbiome and mobile resistome profile of different environments is central to understanding the role of the environment in antimicrobial resistance (AMR), which is one of the urgent threats to global public health. In this study, we demonstrated the use of a rapid (and easily portable) sequencing approach coupled with user-friendly bioinformatics tools, the MinION (Oxford Nanopore Technologies), on the evaluation of the microbial as well as mobile metal and antibiotic resistome profile of semi-rural wastewater. A total of 20 unique phyla, 43 classes, 227 genera, and 469 species were identified in samples collected from the Amherst Wastewater Treatment Plant, both from primary and secondary treated wastewater. Alpha diversity indices indicated that primary samples were significantly richer and more microbially diverse than secondary samples. A total of 1041 ARGs, 68 MRGs, and 17 MGEs were detected in this study. There were more classes of AMR genes in primary than secondary wastewater, but in both cases multidrug, beta-lactam and peptide AMR predominated. Of note, OXA β-lactamases, some of which are also carbapenemases, were enriched in secondary samples. Metal resistance genes against arsenic, copper, zinc and molybdenum were the dominant MRGs in the majority of the samples. A larger proportion of resistome genes were located in chromosome-derived sequences except for mobilome genes, which were predominantly located in plasmid-derived sequences. Genetic elements related to transposase were the most common MGEs in all samples. Mobile or MGE/plasmid-associated resistome genes that confer resistance to last resort antimicrobials such as carbapenems and colistin were detected in most samples. Worryingly, several of these potentially transferable genes were found to be carried by clinically-relevant hosts including pathogenic bacterial species in the orders Aeromonadales, Clostridiales, Enterobacterales and Pseudomonadales. This study demonstrated that the MinION can be used as a metagenomics approach to evaluate the microbiome, resistome, and mobilome profile of primary and secondary wastewater., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Since 2014, biology students at Fort Lewis College have studied the water quality of the Animas River in Durango, Colorado. Environmental microbiology and molecular biology techniques have been employed to study Escherichia coli isolates from the river and to define characteristics of the bacteria related to public health. E. coli was found in the river, as well as in culverts and tributary creeks that drain into the river within the Durango city limits. Concentrations of E. coli in the river occasionally exceeded the US EPA guideline of 126 CFU per 100 mL for recreational water use. Many of the E. coli isolates were able to be grown at 45 °C, an indication of mammalian origin. Unexpectedly, 8% of the isolates contained the intimin ( eae ) gene, a virulence gene characteristic of two pathotypes of E. coli , the enterohemorrhagic and enteropathogenic E. coli. Several isolates tested were resistant to multiple antibiotics commonly used in animal and human medicine. Further study is warranted to determine the source of these bacteria entering the Animas River, and to further characterize the possible disease potential of multi-antibiotic resistant and virulence gene-containing isolates found in a semi-rural/urban setting.

Objective: To evaluate the safety and effectiveness of a wrist-worn peripheral nerve stimulation device in patients with essential tremor (ET) in a single in-office session., Methods: This was a randomized controlled study of 77 ET patients who received either treatment stimulation (N = 40) or sham stimulation (N = 37) on the wrist of the hand with more severe tremor. Tremor was evaluated before and immediately after the end of a single 40-minute stimulation session. The primary endpoint compared spiral drawing in the stimulated hand using the Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) Archimedes spiral scores in treatment and sham groups. Additional endpoints included TETRAS upper limb tremor scores, subject-rated tasks from the Bain and Findley activities of daily living (ADL) scale before and after stimulation as well as clinical global impression-improvement (CGI-I) rating after stimulation., Results: Subjects who received peripheral nerve stimulation did not show significantly larger improvement in the Archimedes spiral task compared to sham but did show significantly greater improvement in upper limb TETRAS tremor scores (p = 0.017) compared to sham. Subject-rated improvements in ADLs were significantly greater with treatment (49% reduction) than with sham (27% reduction; p = 0.001). A greater percentage of ET patients (88%) reported improvement in the stimulation group as compared to the sham group (62%) according to CGI-I ratings (p = 0.019). No significant adverse events were reported; 3% of subjects experienced mild adverse events., Conclusions: Peripheral nerve stimulation in ET may provide a safe, well-tolerated, and effective treatment for transient relief of hand tremor symptoms., (© 2019 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.)

The Little Bighorn River is the primary source of water for water treatment plants serving the local Crow Agency population, and has special significance in the spiritual and ceremonial life of the Crow tribe. Unfortunately, the watershed suffers from impaired water quality, with high counts of fecal coliform bacteria routinely measured during run-off events. A metagenomic analysis was carried out to identify potential pathogens in the river water. The Oxford Nanopore MinION platform was used to sequence DNA in near real time to identify both uncultured and a coliform-enriched culture of microbes collected from a popular summer swimming area of the Little Bighorn River. Sequences were analyzed using CosmosID bioinformatics and, in agreement with previous studies, enterohemorrhagic and enteropathogenic Escherichia coli and other E. coli pathotypes were identified. Noteworthy was detection and identification of enteroaggregative E. coli O104:H4 and Vibrio cholerae serotype O1 El Tor, however, cholera toxin genes were not identified. Other pathogenic microbes, as well as virulence genes and antimicrobial resistance markers, were also identified and characterized by metagenomic analyses. It is concluded that metagenomics provides a useful and potentially routine tool for identifying in an in-depth manner microbial contamination of waterways and, thereby, protecting public health.

The cholera epidemic that occurred in Haiti post-earthquake in 2010 has resulted in over 9000 deaths during the past eight years. Currently, morbidity and mortality rates for cholera have declined, but cholera cases still occur on a daily basis. One continuing issue is an inability to accurately predict and identify when cholera outbreaks might occur. To explore this surveillance gap, a metagenomic approach employing environmental samples was taken. In this study, surface water samples were collected at two time points from several sites near the original epicenter of the cholera outbreak in the Central Plateau of Haiti. These samples underwent whole genome sequencing and subsequent metagenomic analysis to characterize the microbial community of bacteria, fungi, protists, and viruses, and to identify antibiotic resistance and virulence associated genes. Replicates from sites were analyzed by principle components analysis, and distinct genomic profiles were obtained for each site. Cholera toxin converting phage was detected at one site, and Shiga toxin converting phages at several sites. Members of the Acinetobacter family were frequently detected in samples, including members implicated in waterborne diseases. These results indicate a metagenomic approach to evaluating water samples can be useful for source tracking and the surveillance of pathogens such as Vibrio cholerae over time, as well as for monitoring virulence factors such as cholera toxin.

Waterborne diseases continue to take a heavy toll on the global community, with developing nations, and particularly young children carrying most of the burden of morbidity and mortality. Starting with the historical context, this article explores some of the reasons why this burden continues today, despite our advances in public health over the past century or so. While molecular biology has revolutionized our abilities to define the ecosystems and etiologies of waterborne pathogens, control remains elusive. Lack of basic hygiene and sanitation, and failing infrastructure, remain two of the greatest challenges in the global fight against waterborne disease. Emerging risks continue to be the specter of multiple drug resistance and the ease with which determinants of virulence appear to be transmitted between strains of pathogens, both within and outside the human host.

The Little Bighorn River flows through the Crow Indian Reservation in Montana. In 2008, Escherichia coli concentrations as high as 7179 MPN/100 ml were detected in the river at the Crow Agency Water Treatment Plant intake site. During 2008, 2009, and 2012, 10 different serotypes of E. coli, including O157:H7, harboring both intimin and Shiga toxin genes were isolated from a popular swim site of the Little Bighorn River in Crow Agency. As part of a microbial source tracking study, E. coli strains were isolated from river samples as well as from manure collected from a large cattle feeding operation in the upper Little Bighorn River watershed; 23% of 167 isolates of E. coli obtained from the manure tested positive for the intimin gene. Among these manure isolates, 19 were identified as O156:H8, matching the serotype of an isolate collected from a river sampling site close to the cattle feeding area.

Bile salts exhibit potent antibacterial properties, acting as detergents to disrupt cell membranes and as DNA-damaging agents. Although bacteria inhabiting the intestinal tract are able to resist bile's antimicrobial effects, relatively little is known about how bile influences virulence of enteric pathogens. Escherichia coli O157:H7 is an important pathogen of humans, capable of causing severe diarrhea and more serious sequelae. In this study, the transcriptome response of E. coli O157:H7 to bile was determined. Bile exposure induced significant changes in mRNA levels of genes related to virulence potential, including a reduction of mRNA for the 41 genes making up the locus of enterocyte effacement (LEE) pathogenicity island. Bile treatment had an unusual effect on mRNA levels for the entire flagella-chemotaxis regulon, resulting in two- to four-fold increases in mRNA levels for genes associated with the flagella hook-basal body structure, but a two-fold decrease for "late" flagella genes associated with the flagella filament, stator motor, and chemotaxis. Bile salts also caused increased mRNA levels for seventeen genes associated with iron scavenging and metabolism, and counteracted the inhibitory effect of the iron chelating agent 2,2'-dipyridyl on growth of E. coli O157:H7. These findings suggest that E. coli O157:H7 may use bile as an environmental signal to adapt to changing conditions associated with the small intestine, including adaptation to an iron-scarce environment.

The purpose of our study was to investigate whether shoulder taping affects shoulder kinematics in injured and previously injured overhead athletes during a seated throw. Twenty-six overhead college athletes threw a handball three times with and without tape, while seated on a chair. An 8-camera Vicon Motion Capture system recorded markers placed on the upper limb and trunk during each of the throwing conditions. Scaled musculoskeletal models of the upper limb were created using OpenSim and inverse kinematics used to obtain relevant joint angles. Shoulder taping had no main effect on external (ER) and internal (IR) rotation range (ROM) of the shoulder, but a significant interaction effect was found (p = 0.003 and 0.02, respectively), depending on previous injury status, whereby both the ER and IR ROM of the shoulder in the group of previously injured athletes decreased when taped (143-138° and 54-51°, respectively), but increased in the group who had never been injured (131-135° and 42-44°, respectively). Maximum abduction range and ball velocity were not affected by the application of shoulder taping, regardless of previous injury status. Thus, application of shoulder taping has a differential effect on maximum shoulder ER and IR ROM during throwing depending on previous injury status. These findings have implications for returning athletes to sport after injury and for screening athletes at risk of injury., (Copyright © 2011 Orthopaedic Research Society.)

Escherichia coli serotype O157:H7 was detected among bacteria collected from the Ganges River. O157:H7 isolates tested positive for stx(1), stx(2), and eae gene sequences. Identification of potentially pathogenic isolates from extensively used source water indicates that O157:H7 may be a significant but as yet underacknowledged public health concern in India.

In Varanasi, India, an estimated 200 million liters daily or more of untreated human sewage is discharged into the Ganges River. River water monitoring over the past 12 years has demonstrated faecal coliform counts up to 10(8) MPN (most probable number) per 100 ml and biological oxygen demand levels averaging over 40 mg/l in the most polluted part of the river in Varanasi. A questionnaire-based survey was used to estimate water-borne and enteric disease incidence and study river use among resident users of the Ganges River in Varanasi. The overall rate of water-borne/enteric disease incidence, including acute gastrointestinal disease, cholera, dysentery, hepatitis-A, and typhoid, was estimated to be about 66% during the one-year period prior to the survey. Logistic regression analysis revealed significant associations between water-borne/enteric disease occurrence and the use of the river for bathing, laundry, washing eating utensils, and brushing teeth. Thirty-three cases of cholera were identified among families exposed to washing clothing or bathing in the Ganges while no cholera cases occurred in unexposed families. Other exposure factors such as lack of sewerage and toilets at residence, children defecating outdoors, poor sanitation, low income and low education levels also showed significant associations with enteric disease outcome. This study provides an estimate of water-borne/enteric disease incidence and identifies possible risk factors for residents who live by and use the Ganges River in Varanasi.

The scope of services provided by the Staff Development Department or clinical educators in healthcare settings includes, but is not limited to, employee orientation, continuing education, and competency assessment. The critical issue of ascertaining competency of nursing staff in medication dosage calculation encompasses each of these functions. The authors describe the process of pilot testing a dosage calculation test in an ambulatory care setting, adapting it based on feedback, using it with orientees and current staff, and using the educational process with nurses needing assistance in dosage calculation.

The abilities of rodent tumor cell lines; B16BL6, ND and LT dietary variants of B16BL6, +SA, RT7-4bs and RT7-4bLs to invade composite collagen I gels containing heparin, chemically modified heparins, heparan sulfate, chondroitin sulfate, hyaluronic acid, dextran, dextran sulfate, laminin and collagen IV were investigated, and compared to the invasion of plain collagen I gels. The presence of heparin or heparan sulfate most generally promoted tumor cell invasion of the gels, with more aggressive invasion being noted for the more metastatic variants examined. Of the chemically modified heparins tested, carboxyl-reduced heparin promoted matrix invasion by B16BL6 and +SA cells to the greatest degree. Hyaluronic acid marginally promoted invasion by +SA and RT7-4bs primary cells while, in these collagen I based gels laminin only promoted matrix invasion by primary +SA cells to a very limited degree. The tumor cell lines attached relatively poorly to heparan sulfate substrates compared to the other glycosaminoglycans tested, and the primary tumor cell lines also attached relatively poorly to collagen I. As expected, highly metastatic variants showed greater attachment to laminin than did their less metastatic counterparts. Apart from the negative correlation of cellular attachment to heparan sulfate substrates with invasiveness towards heparan sulfate containing gels, no other relationships emerged linking attachment rates with invasive activities for particular complex gel compositions. Our results suggest an important role for heparan sulfate, and possibly also tissue heparin, in promoting tumor cell invasion of extracellular matrices. Results from complex gels containing dextran or dextran sulfate failed to support the hypothesis that GAG sulfation is important to cellular invasion. The activity of the chemically modified heparins in promoting invasion, when present as components of these model matrices, suggests that part of the anti-metastatic activity of these compounds, when preincubated with tumor cells prior to intravenous inoculation, could result from interference with tumor cell extravasation.

To determine the effects of blood transfusions on splenic function in older patients with sickle cell anemia, we investigated splenic function in 12 patients who had had cerebrovascular accidents and who were being treated at two collaborating centers using different transfusion protocols. Splenic function was assessed by radionuclide scan and pocked erythrocyte count. Patients were 6 to 18 years of age and had been receiving transfusions for 7 months to 10 years (median 4.2 years). Of the 12 children, five had normal or increased splenic size and function (normal scan and normal or minimally elevated pocked erythrocyte count). All were receiving intensive transfusion therapy, with the aim of maintaining the hemoglobin S level at less than 20%. The other seven patients had abnormal splenic function (absent radionuclide uptake and elevated pocked erythrocyte count); each was receiving less intensive transfusion therapy, with the pretransfusion hemoglobin S level usually at 30% to 40%. No patient developed bacterial septicemia while receiving hypertransfusion therapy. We conclude that splenic function during a long-term transfusion program is variable, depending in part on the "intensity" of transfusion therapy. Apparent splenic involution and fibrosis may be a reversible event in some patients.

We have examined the nature of biochemical degradation of an isolated basement membrane matrix (bovine lens capsule) using different methodologies. The first strategy was quantitation of the release of surface-bound 125I and a second the documentation by SDS-PAGE of the appearance of putative cleavage products and the loss of high-molecular-weight components from the matrix. Basement membrane matrix bands resolved on SDS-PAGE were identified by their protease sensitivities as well as by Western immunoblots using monoclonal antibodies developed for this study. Radioiodinated components were found predominantly at positions on the gel equivalent to 160-200 kd and 400 kd proteins. Since these labeled moieties were sensitive to bacterial collagenase digestion and stained with anticollagen type IV antibodies, they were determined to represent various configurations of collagen type IV. Several other lower-molecular-weight bands also stained with the anticollagen IV antibodies. Monoclonal antibodies reactive with laminin exhibited a complex staining pattern on the gels, which included the expected 200 and 400 kd components. We confirmed that lens capsule basement membrane contained only a single heparan sulfate glycosaminoglycan species, and tumor cell-induced glycosaminoglycan degradation within the basement membrane matrix was detected using cellulose acetate electrophoresis. Distinctive putative cleavage products were resolved on SDS-PAGE gels from matrices subjected to digestion by a variety of purified proteases as well as by metastatic tumor cells or their conditioned media. Tumor cells of different histiotypes produced different characteristic cleavage patterns, suggestive of the existence of several pathways of matrix degradation. Overall, primary tumor cells exhibited a greater degradative activity towards the basement membrane matrix than did long-term tissue culture-passaged cells. The same tumor cell line could exhibit considerably different patterns of both protein and glycosaminoglycan degradation depending on recent culture history. The relevance of these biochemical studies to the pathogenesis of malignant neoplasms is shown by: 1) the evaluation of degradative activities of B16 tumor cell populations exhibiting enhanced lung-colonizing phenotypes, and 2) the ability of a known antimetastatic moiety with antiprotease activity (Haementeria leech species salivary gland extract) to protect matrix components from degradation by tumor cell-conditioned medium.

Three related mouse mammary cell lines were cultured in collagen gels and assayed for growth factor responsiveness and interaction via soluble factors. The CL-S1 cell line is nontumorigenic and grows poorly in collagen gel culture. The +SA and -SA cell lines exhibit different degrees of malignant behavior in vivo and have different growth properties in vitro. In collagen gel culture, +SA growth was stimulated by serum but not by epidermal growth factor (EGF), whereas both serum and EGF were required for optimal growth of -SA cells of early passage number as well as CL-S1 cells. -SA cells of later passage repeatedly exhibited a change so as to no longer require serum while retaining EGF responsiveness. [125I]EGF binding analyses indicated that CL-S1 cells bound EGF with less affinity than did -SA cells whereas +SA cells bound almost no ligand. When cell lines were maintained in separate collagen gels but shared the same culture medium, growth of +SA or -SA cells was slightly enhanced in the presence of CL-S1 cells and -SA cell growth was enhanced by the presence of +SA cells. Using the normal rat kidney fibroblast line NRK (clone 49F) as an indicator, serum-containing conditioned media from each cell line and from each pair of cell lines cultured in collagen gels were tested for transforming growth factor (TGF) activity. Both the -SA and CL-S1 lines tested positive for TGF-alpha production and possibly released a TGF-beta activity. These results suggest mechanisms by which cell populations in and around tumors can modify one another's growth characteristics.