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1. Gastroenterologist and nurse management of symptoms after pelvic radiotherapy for cancer: an economic evaluation of a clinical randomized controlled trial (the ORBIT study)

Author: Jordan J, Gage H, Benton B, Lalji A, Norton C, and Andreyev HJN
Subjects: Pelvic radiotherapy, Algorithmic care, Gastroenterologist, Clinical nurse specialist, Medicine (General), R5-920, Therapeutics. Pharmacology, RM1-950
Abstract: Jake Jordan,1 Heather Gage,1 Barbara Benton,2 Amyn Lalji,2 Christine Norton,3 H Jervoise N Andreyev2 1Surrey Health Economics Centre, School of Economics, University of Surrey, Guildford, 2Gastrointestinal Unit, Royal Marsden NHS Foundation Trust, 3Florence Nightingale Faculty of Nursing and Midwifery, King’s College, London, UK Background: Over 20 distressing gastrointestinal symptoms affect many patients after pelvic radiotherapy, but in the United Kingdom few are referred for assessment. Algorithmic-based treatment delivered by either a consultant gastroenterologist or a clinical nurse specialist has been shown in a randomized trial to be statistically and clinically more effective than provision of a self-help booklet. In this study, we assessed cost-effectiveness.Methods: Outcomes were measured at baseline (pre-randomization) and 6 months. Change in quality-adjusted life years (QALYs) was the primary outcome for the economic evaluation; a secondary analysis used change in the bowel subset score of the modified Inflammatory Bowel Disease Questionnaire (IBDQ-B). Intervention costs, British pounds 2013, covered visits with the gastroenterologist or nurse, investigations, medications and treatments. Incremental outcomes and incremental costs were estimated simultaneously using multivariate linear regression. Uncertainty was handled non-parametrically using bootstrap with replacement.Results: The mean (SD) cost of treatment was £895 (499) for the nurse and £1101 (567) for the consultant. The nurse was dominated by usual care, which was cheaper and achieved better outcomes. The mean cost per QALY gained from the consultant, compared to usual care, was £250,455; comparing the consultant to the nurse, it was £25,875. Algorithmic care produced better outcomes compared to the booklet only, as reflected in the IBDQ-B results, at a cost of ~£1,000.Conclusion: Algorithmic treatment of radiation bowel injury by a consultant or a nurse results in significant symptom relief for patients but was not found to be cost-effective according to the National Institute for Health and Care Excellence (NICE) criteria. Keywords: pelvic radiotherapy, algorithmic care, gastroenterologist, clinical nurse specialist
Published: 2017

2. A novel FK506- and rapamycin-binding protein (FPR3 gene product) in the yeast Saccharomyces cerevisiae is a proline rotamase localized to the nucleolus.

Author: Benton, B, Zang, J, and THORNER, Jeremy W.
Subjects: Amino Acid Isomerases, Amino Acid Sequence, Base Sequence, Carrier Proteins, Cell Nucleolus, Cloning, Molecular, DNA, Fungal, Escherichia coli, Genes, Fungal, Genotype, Heat-Shock Proteins, Molecular Sequence Data, Mutagenesis, Site-Directed, Oligodeoxyribonucleotides, Peptidylprolyl Isomerase, Polyenes, Polymerase Chain Reaction, Recombinant Proteins, Restriction Mapping, Saccharomyces cerevisiae, Sequence Deletion, Sequence Homology, Amino Acid, Sirolimus, Tacrolimus, Tacrolimus Binding Proteins
Abstract: The gene (FPR3) encoding a novel type of peptidylpropyl-cis-trans-isomerase (PPIase) was isolated during a search for previously unidentified nuclear proteins in Saccharomyces cerevisiae. PPIases are thought to act in conjunction with protein chaperones because they accelerate the rate of conformational interconversions around proline residues in polypeptides. The FPR3 gene product (Fpr3) is 413 amino acids long. The 111 COOH-terminal residues of Fpr3 share greater than 40% amino acid identity with a particular class of PPIases, termed FK506-binding proteins (FKBPs) because they are the intracellular receptors for two immunosuppressive compounds, rapamycin and FK506. When expressed in and purified from Escherichia coli, both full-length Fpr3 and its isolated COOH-terminal domain exhibit readily detectable PPIase activity. Both fpr3 delta null mutants and cells expressing FPR3 from its own promoter on a multicopy plasmid have no discernible growth phenotype and do not display any alteration in sensitivity to the growth-inhibitory effects of either FK506 or rapamycin. In S. cerevisiae, the gene for a 112-residue cytosolic FKBP (FPR1) and the gene for a 135-residue ER-associated FKBP (FPR2) have been described before. Even fpr1 fpr2 fpr3 triple mutants are viable. However, in cells carrying an fpr1 delta mutation (which confers resistance to rapamycin), overexpression from the GAL1 promoter of the C-terminal domain of Fpr3, but not full-length Fpr3, restored sensitivity to rapamycin. Conversely, overproduction from the GAL1 promoter of full-length Fpr3, but not its COOH-terminal domain, is growth inhibitory in both normal cells and fpr1 delta mutants. In fpr1 delta cells, the toxic effect of Fpr3 overproduction can be reversed by rapamycin. Overproduction of the NH2-terminal domain of Fpr3 is also growth inhibitory in normal cells and fpr1 delta mutants, but this toxicity is not ameliorated in fpr1 delta cells by rapamycin. The NH2-terminal domain of Fpr3 contains long stretches of acidic residues alternating with blocks of basic residues, a structure that resembles sequences found in nucleolar proteins, including S. cerevisiae NSR1 and mammalian nucleolin. Indirect immunofluorescence with polyclonal antibodies raised against either the NH2- or the COOH-terminal segments of Fpr3 expressed in E. coli demonstrated that Fpr3 is located exclusively in the nucleolus.
Published: 1994

3. A prospective prostate cancer screening programme for men with pathogenic variants in mismatch repair genes (IMPACT): initial results from an international prospective study.

Author: Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., Eeles R.A., Bancroft E.K., Page E.C., Brook M.N., Thomas S., Taylor N., Pope J., McHugh J., Jones A.-B., Karlsson Q., Merson S., Ong K.R., Hoffman J., Huber C., Maehle L., Grindedal E.M., Stormorken A., Evans D.G., Rothwell J., Lalloo F., Brady A.F., Bartlett M., Snape K., Hanson H., James P., McKinley J., Mascarenhas L., Syngal S., Ukaegbu C., Side L., Thomas T., Barwell J., Teixeira M.R., Izatt L., Suri M., Macrae F.A., Poplawski N., Chen-Shtoyerman R., Ahmed M., Musgrave H., Nicolai N., Greenhalgh L., Brewer C., Pachter N., Spigelman A.D., Azzabi A., Helfand B.T., Halliday D., Buys S., Ramon y Cajal T., Donaldson A., Cooney K.A., Harris M., McGrath J., Davidson R., Taylor A., Cooke P., Myhill K., Hogben M., Aaronson N.K., Ardern-Jones A., Bangma C.H., Castro E., Dearnaley D., Dias A., Dudderidge T., Eccles D.M., Green K., Eyfjord J., Falconer A., Foster C.S., Gronberg H., Hamdy F.C., Johannsson O., Khoo V., Lilja H., Lindeman G.J., Lubinski J., Axcrona K., Mikropoulos C., Mitra A.V., Moynihan C., Ni Raghallaigh H., Rennert G., Collier R., Adams L., Adlard J., Alfonso R., Ali S., Andrew A., Araujo L., Azam N., Ball D., Barker Q., Basevitch A., Benton B., Berlin C., Bermingham N., Biller L., Bloss A., Bradford M., Bradshaw N., Branson A., Brendler C., Brennan M., Bulman B., Burgess L., Cahill D., Callard A., Calvo Verges N., Cardoso M., Carter V., Catanzaro M., Chamberlain A., Chapman C., Chong M., Clark C., Clowes V., Cogley L., Cole T., Compton C., Conner T., Cookson S., Cornford P., Costello P., Coulier L., Davies M., Dechet C., DeSouza B., Devlin G., Douglas F., Douglas E., Dudakia D., Duncan A., Ellery N., Everest S., Freemantle S., Frydenberg M., Fuller D., Gabriel C., Gale M., Garcia L., Gay S., Genova E., George A., Georgiou D., Gisbert A., Gleeson M., Glover W., Gnanapragasam V., Goff S., Goldgar D., Goncalves N., Goodman S., Gorrie J., Gott H., Grant A., Gray C., Griffiths J., Gupwell K., Gurasashvili J., Hanslien E., Haraldsdottir S., Hart R., Hartigan C., Hawkes L., Heaton T., Henderson A., Henrique R., Hilario K., Hill K., Hulick P., Hunt C., Hutchings M., Ibitoye R., Inglehearn T., Ireland J., Islam F., Ismail S., Jacobs C., James D., Jenkins S., Jobson I., Johnstone A., Jones O., Josefsberg Ben-Yehoshua S., Kaemba B., Kaul K., Kemp Z., Kinsella N., Klehm M., Kockelbergh R., Kohut K., Kosicka-Slawinska M., Kulkarni A., Kumar P., Lam J., LeButt M., Leibovici D., Lim R., Limb L., Lomas C., Longmuir M., Lopez C., Magnani T., Maia S., Maiden J., Male A., Manalo M., Martin P., McBride D., McGuire M., McMahon R., McNally C., McVeigh T., Melzer E., Mencias M., Mercer C., Mitchell G., Mora J., Morton C., Moss C., Murphy M., Murphy D., Mzazi S., Nadolski M., Newlin A., Nogueira P., O'Keefe R., O'Toole K., O'Connell S., Ogden C., Okoth L., Oliveira J., Paez E., Palou J., Park L., Patel N., Paulo Souto J., Pearce A., Peixoto A., Perez K., Petelin L., Pichert G., Poile C., Potter A., Preitner N., Purnell H., Quinn E., Radice P., Rankin B., Rees K., Renton C., Richardson K., Risby P., Rogers J., Ruderman M., Ruiz A., Sajoo A., Salvatore N., Sands V., Sanguedolce F., Sattar A., Saunders K., Schofield L., Scott R., Searle A., Sehra R., Selkirk C., Shackleton K., Shanley S., Shaw A., Shevrin D., Shipman H., Sidat Z., Siguake K., Simon K., Smyth C., Snadden L., Solanky N., Solomons J., Sorrentino M., Stayner B., Stephenson R., Stoffel E., Thomas M., Thompson A., Tidey L., Tischkowitz M., Torokwa A., Townshend S., Treherne K., Tricker K., Trinh Q.-D., Tripathi V., Turnbull C., Valdagni R., Van As N., Venne V., Verdon L., Vitellaro M., Vogel K., Walker L., Watford A., Watt C., Weintroub I., Weiss S., Weissman S., Weston M., Wiggins J., Wise G., Woodhouse C., Yesildag P., Youngs A., Yurgelun M., Zollo F., Offman J., Kote-Jarai Z., and Eeles R.A.
Abstract: Background: Lynch syndrome is a rare familial cancer syndrome caused by pathogenic variants in the mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, predominantly colorectal and endometrial cancer. Data are emerging that pathogenic variants in mismatch repair genes increase the risk of early-onset aggressive prostate cancer. The IMPACT study is prospectively assessing prostate-specific antigen (PSA) screening in men with germline mismatch repair pathogenic variants. Here, we report the usefulness of PSA screening, prostate cancer incidence, and tumour characteristics after the first screening round in men with and without these germline pathogenic variants. Method(s): The IMPACT study is an international, prospective study. Men aged 40-69 years without a previous prostate cancer diagnosis and with a known germline pathogenic variant in the MLH1, MSH2, or MSH6 gene, and age-matched male controls who tested negative for a familial pathogenic variant in these genes were recruited from 34 genetic and urology clinics in eight countries, and underwent a baseline PSA screening. Men who had a PSA level higher than 3.0 ng/mL were offered a transrectal, ultrasound-guided, prostate biopsy and a histopathological analysis was done. All participants are undergoing a minimum of 5 years' annual screening. The primary endpoint was to determine the incidence, stage, and pathology of screening-detected prostate cancer in carriers of pathogenic variants compared with non-carrier controls. We used Fisher's exact test to compare the number of cases, cancer incidence, and positive predictive values of the PSA cutoff and biopsy between carriers and non-carriers and the differences between disease types (ie, cancer vs no cancer, clinically significant cancer vs no cancer). We assessed screening outcomes and tumour characteristics by pathogenic variant status. Here we present results from the first round of PSA screening in the IMPACT study. This
Published: 2022

4. The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening

Author: Benafif, S, Ni Raghallaigh, H, McGrowder, E, Saunders, EJ, Brook, MN, Saya, S, Rageevakumar, R, Wakerell, S, James, D, Chamberlain, A, Taylor, N, Hogben, M, Benton, B, D'Mello, L, Myhill, K, Mikropoulos, C, Bowen-Perkins, H, Rafi, I, Ferris, M, Beattie, A, Kuganolipava, S, Sevenoaks, T, Bower, J, Kumar, P, Hazell, S, deSouza, NM, Antoniou, A, Bancroft, E, Kote-Jarai, Z, Eeles, R, Benafif, S, Ni Raghallaigh, H, McGrowder, E, Saunders, EJ, Brook, MN, Saya, S, Rageevakumar, R, Wakerell, S, James, D, Chamberlain, A, Taylor, N, Hogben, M, Benton, B, D'Mello, L, Myhill, K, Mikropoulos, C, Bowen-Perkins, H, Rafi, I, Ferris, M, Beattie, A, Kuganolipava, S, Sevenoaks, T, Bower, J, Kumar, P, Hazell, S, deSouza, NM, Antoniou, A, Bancroft, E, Kote-Jarai, Z, and Eeles, R
Abstract: OBJECTIVES: To assess the feasibility and uptake of a community-based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men. SUBJECTS AND METHODS: Healthy males aged 55-69 years were invited to participate via their general practitioners (GPs). Saliva samples were collected via mailed collection kits. After DNA extraction, genotyping was conducted using a study specific assay. Genetic risk was based on genotyping 130 germline PCa risk single nucleotide polymorphisms (SNPs). A polygenic risk score (PRS) was calculated for each participant using the sum of weighted alleles for 130 SNPs. Study participants with a PRS lying above the 90th centile value were invited for PCa screening by prostate magnetic resonance imaging (MRI) and biopsy. RESULTS: Invitation letters were sent to 1434 men. The overall study uptake was 26% (375/1436) and 87% of responders were eligible for study entry. DNA genotyping data were available for 297 men and 25 were invited for screening. After exclusions due to medical comorbidity/invitations declined, 18 of 25 men (72%) underwent MRI and biopsy of the prostate. There were seven diagnoses of PCa (38.9%). All cancers were low-risk and were managed with active surveillance. CONCLUSION: The BARCODE1 Pilot has shown this community study in the UK to be feasible, with an overall uptake of 26%. The main BARCODE1 study is now open and will recruit 5000 men. The results of BARCODE1 will be important in defining the role of genetic profiling in targeted PCa population screening. Patient Summary What is the paper about? Very few prostate cancer screening programmes currently exist anywhere in the world. Our pilot study investigated if men in the UK would find it acceptable to have a genetic test based on a saliva sample to examin
Published: 2022

5. 32 Assessment of Dry-Aged Beef from Commercial Aging Locations Across the United States

Author: Jessica M Lancaster, Phillip D. Bass, William J. Price, Kizkitza Insausti, J.A. Nasados, Jessie B Van Buren, Brianna J. Buseman, Tanya M. Weber, Benton B Glaze, Jaxon H. Smart, and Michael J. Colle
Subjects: Genetics, Oral Presentations, Animal Science and Zoology, General Medicine, Food Science
Abstract: Dry-aging is a practice that involves storing meat at refrigerated temperatures without protective packaging. Despite the increase in dry-aged beef popularity, relatively little is known about commercial dry-aging parameters. Thus, the objectives of this study were to determine dry-aging parameters of commercial aging facilities and their influence on eating quality (acceptability, flavor, tenderness, and juiciness) of dry-aged beef from locations across the United States. Sixty-six Certified Angus Beef® brand bone-in beef strip loins (IMPS #175) were randomly assigned to ten commercial dry-aging facilities across the United States. An additional six strip loins were wet-aged for 45-days as a negative control. Strip loins were shipped overnight to aging locations where a 45-day dry aging period transpired before being returned for subsequent analysis, upon completion of aging. Objective color, pH, and water activity were measured post aging, at the time of processing. Strip loins were then fabricated, and steaks were vacuum packaged and frozen until further analysis. Intrinsic quality parameters objective color (L*, a*, b*), pH, and water activity were not different (P > 0.05) between strip loins aged 45 days by location. Cooler conditions including temperature, percent relative humidity, and air speed were different (P < 0.01) across aging locations. Pacific Northwest consumer panelists indicated a difference in overall acceptability (P < 0.01), tenderness (P = 0.01), and flavor (P < 0.01) based on aging location. Additionally, consumers detected (P < 0.01) unique dry-aging flavors for individual aging locations including cheesy and nutty attributes. Research indicates individual dry-aging facility conditions aid in producing unique dry-aged beef products according to U.S. consumers from the Pacific Northwest Region.
Published: 2021

6. 32 Assessment of Dry-Aged Beef from Commercial Aging Locations Across the United States

Author: Lancaster, Jessica M, primary, Smart, Jaxon, additional, Buseman, Brianna, additional, Van Buren, Jessie B, additional, Weber, Tanya, additional, Insausti, Kizkitza, additional, Nasados, James, additional, Glaze, Benton B, additional, Price, William, additional, Colle, Michael, additional, and Bass, Phillip, additional
Published: 2021
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7. Telavancin targets the bacterial membrane of Staphylococcus aureus: analysis of membrane effects by flow cytometry: O256

Author: Lunde, C., Renelli, M., Janc, J., Mammen, M., Humphrey, P., and Benton, B.
Published: 2007

8. Telavancin inhibits peptidoglycan biosynthesis through preferential targeting of transglycosylation: evidence for a multivalent interaction between telavancin and lipid II: O258

Author: Benton, B., Breukink, E., Visscher, I., Debabov, D., Lunde, C., Janc, J., Mammen, M., and Humphrey, P.
Published: 2007

9. Health in Fragile States: Opinion Piece

Author: Benton, B, Handuleh, J, Harris, K, Maruthappu, M, Patel, P, Godman, B, and Finlayson, A
Published: 2014

10. Protection Against the Vesicant Chemical Warfare Agent Sulfur Mustard: Therapeutics Utilizing Apoptosis Inhibitors

Author: ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD RESEARCH DIVISION, Ray, R., Benton, B. J., Hauck, S. L., Carpin, C., Rosenthal, D. S., ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD RESEARCH DIVISION, Ray, R., Benton, B. J., Hauck, S. L., Carpin, C., and Rosenthal, D. S.
Abstract: Sulfur mustard (SM, bis-(2-chloroethyl) sulfide), commonly called mustard gas, is a vesicant chemical warfare agent and a potential terrorism agent. SM is relatively easy to make and to deploy, which makes this chemical most likely to be used. SM exposure causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract. Therefore, developing an effective medical countermeasure to protect against the dermal, ocular and airway injuries due to this dreaded chemical agent is an urgent priority of the US Army. SM pathophysiology is consistent with epithelial cell damage, particularly basal cell apoptosis. SM-induced apoptosis may occur via multiple pathways dependent on one or more of the following: (a) abnormal Ca2+ homeostasis, (b) disturbed cellular bioenergetics, and (c) Fas (death receptor) response. Apoptosis pathways are characterized by the involvement of the pathway-specific caspases (cysteine aspartase). We determined caspase activity by assay of fluorogenic caspase type-specific peptide substrate hydrolysis. We studied caspase processing, i.e., proteolytic conversion of procaspase to active caspase by immunoblot analyses utilizing caspase type-specific antibodies. Our results in cell culture models of both human epidermal keratinocytes and human airway epithelial cells indicated that SM activates (a) caspase-9, an indicator of the Ca2+/CaM-mediated mitochondrial pathway, (b) caspase-8, a marker for the Fas-mediated pathway, and (c) caspase-3, the executioner caspase involved in both pathways. A peptide caspase inhibitor, specific for caspase-3 (ACDEVD-CHO), added to cells prior to SM decreased apoptosis. These observations suggest apoptosis as a mechanism of SM toxicity and caspase inhibitors as prospective medical countermeasures., See also ADM002075. Presented at the Army Science Conference (25th) held in Orlando, Florida on 27-30 November 2006. The original document contains color images.
Published: 2006

11. Investigation of Hair Follicle and Plasma Biomarkers for Low-Level VX Vapor Exposure

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, LaFiandra, E. M., Chambers, A. E., Horsmon, J., Valdes, J. J., Sekowski, J. W., Benton, B., Horsmon, M., Mioduszewski, R., Thomson, S., Evans, C., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, LaFiandra, E. M., Chambers, A. E., Horsmon, J., Valdes, J. J., Sekowski, J. W., Benton, B., Horsmon, M., Mioduszewski, R., Thomson, S., and Evans, C.
Abstract: Currently, there are no field-ready and expedient assays able to determine whether someone has been exposed to very low-level chemical warfare agent (CWA). Furthermore, if it were known that a person had been exposed, there is a paucity of information regarding the potential for transient or persistent neurological or other injuries. While our laboratory is working to address both of these problems, our recent work toward finding a more expedient method of detecting low-level agent exposure is addressed in this manuscript. Our laboratory has used two approaches on three different tissues in order to identify molecular indicators (biomarkers) of exposure to VX, an organophosphate (OP) nerve agent. The work described in this manuscript utilizes a whole mount immunohistochemistry (IHC) technique on whisker hair follicles and liquid chromatography coupled to mass spectrometry (LC/MS) on blood plasma to mine for metabolic biomarkers of VX exposure. To date, the work has identified several promising proteins in the follicle and a panel of interesting plasma metabolite markers in the plasma and liver that can discriminate VX exposure versus air as well as level of VX exposure., See also ADM002075. Presented at the Army Science Conference (25th) held in Orlando, Florida on 27-30 November 2006. The original document contains color images.
Published: 2006

12. Tolerance to the Ocular and Cardiovascular Effects of Repeated Low-Level Exposure to Sarin Vapor

Author: NATIONAL ACADEMY OF SCIENCES-NATIONAL RESEARCH COUNCIL WASHINGTON DC, Dabisch, P. A., To, S. D., Kerut, E. K., Miller, D. B., Burnett, D. C., Jakubowski, E. M., Muse, W. T., Davis, E. A., Benton, B. J., Hulet, S. W., NATIONAL ACADEMY OF SCIENCES-NATIONAL RESEARCH COUNCIL WASHINGTON DC, Dabisch, P. A., To, S. D., Kerut, E. K., Miller, D. B., Burnett, D. C., Jakubowski, E. M., Muse, W. T., Davis, E. A., Benton, B. J., and Hulet, S. W.
Abstract: Inhibition of acetylcholinesterase (AChE) by the nerve agent sarin (GB) results in accumulation of acetylcholine and excessive cholinergic stimulation. Little data exists in the literature regarding the effects of low-level repeated exposure to GB vapor. In the present study male rats were exposed to multiple low-level inhalation exposures to GB vapor. The data from the present study demonstrate that multiple inhalation exposures to GB vapor result in tolerance to the ocular and autonomic effects of GB vapor. While the observed decrease in the potency of GB in rats cannot he attributed to a reduction in the inhibitory effect of GB additional experiments are needed to determine the exact mechanism of the tolerance observed., See also ADM001736, Proceedings for the Army Science Conference (24th) held on 29 November - 2 December 2004 in Orlando, Florida.
Published: 2004

13. Low-Level Inhalation Exposure to Chemical Nerve Agent Vapor Induces Expression of Neuronal Apoptosis and Regeneration Genes

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Sekowski, J. W., Orehek, M. A., Bucher, J., Vahey, M., Nau, M., Horsmon, M. S., Menking, D., Whalley, C., Benton, B., Mioduszewski, R., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Sekowski, J. W., Orehek, M. A., Bucher, J., Vahey, M., Nau, M., Horsmon, M. S., Menking, D., Whalley, C., Benton, B., and Mioduszewski, R.
Abstract: For over a decade following end of the first Gulf War in 1991, there has been increasing concern to understand the immediate and persistent effects of sub-acute and low-level exposures to chemical warfare agents. Although low-level exposures may not cause obvious pathology at the time of exposure, they may cause molecular-level toxic injuries in the brain and other vital organ systems. The work described in this manuscript was designed to the measure the gene and protein expression alterations in the brains of male and female rats exposed to sub- and peri-miotic levels of the aerosolized nerve agents sarin (GB) and cyclosarin (GF). Gene expression was assessed using DNA microarray analysis. The microarray data were verified by real-time RT -PCR and Western immunoblotting were possible., See also ADM001736, Proceedings for the Army Science Conference (24th) held on 29 November - 2 December 2004 in Orlando, Florida., The original document contains color images.
Published: 2004

14. Toxic Effects of a Whole-Body Inhalation Sarin (GR) Vapor Exposure in the Gottingen Minipig

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Hulet, S. W., Jakubowski, E. M., Dabisch, P. A., Foster, J. S., Miller, D. B., Benton, B. J., Muse, W. T., Way, R. A., Edwards, J. L., McGuire, J.M., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Hulet, S. W., Jakubowski, E. M., Dabisch, P. A., Foster, J. S., Miller, D. B., Benton, B. J., Muse, W. T., Way, R. A., Edwards, J. L., and McGuire, J.M.
Abstract: Exposure to nerve agent vapors may result in a diverse array of clinical responses including threshold effects to lethality over a relatively small range of dosages. In order to assess the toxic hazards of such exposures and define chemical defense materiel requirements, it is essential to fill gaps in toxicological databases that define the physiological progression; from the first noticeable effect (miosis) to potentially fatal effects of inhalation exposure. Although there are numerous published works investigating the progression of toxic signs elicited by sarin (GB) exposures, both by accidental exposures and in research applications, never has there been a systematic whole-body inhalation study investigating the effects on multiple systems in real-time. While information gleamed from accidental inhalation exposures provides valuable insights on the short and long term sequalae of the exposure, by their nature they do not provide this information until after the subject has been removed from imminent danger, detoxified, and stabilized. In the past, the logistical problems encountered when performing whole-body inhalation experiments with nerve agents have severely limited the ability to collect data in real-time during the exposure. Therefore, the majority of work encompassing nerve agent studies and real-time data collection involves subcutaneous or intravenous injections as the delivery route. While the data collected from these studies is invaluable for assessing medical treatments and short and long-term effects from the agents, the time course of effects (from first evidence of agent in the systemic circulation, to onset of signs, to progression from mild to moderate to severe signs, to death) and compartmental distribution is vastly different. Additionally, and most importantly, they do not address the most likely route of exposure on the battlefield, i.e., inhalation., The original document contains color images. See also ADM001736, Proceedings for the Army Science Conference (24th) Held on 29 November -2 December 2004 in Orlando, Florida., The original document contains color images.
Published: 2004

15. Low-Level Effects of VX Vapor Exposure on Pupil Diameter and Cholinesterase Levels in Rats

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Benton, B. J., Crosier, R. B., Sommerville, D. R., Jakubowski, E. M., Jr., Anthony, J. S., Jr., Scotto, J., Hulet, S. W., Whalley, C. E., Crouse, C. L., Matson, K. L., Miller, D. B., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Benton, B. J., Crosier, R. B., Sommerville, D. R., Jakubowski, E. M., Jr., Anthony, J. S., Jr., Scotto, J., Hulet, S. W., Whalley, C. E., Crouse, C. L., Matson, K. L., and Miller, D. B.
Abstract: The median effective concentrations (EC sub 50's) for miosis in male and female rats exposed to VX vapor for 10, 60 and 240 min were estimated using whole body vapor exposures conducted in a 750 liter dynamic airflow inhalation chamber. Miosis was defined as at least a 50% reduction in pupil diameter relative to baseline measurements. Results show that the median effective dosages (ECt sub 50) for miosis are approximately an order of magnitude lower than the calculated ECt sub 50 values for both GB and GF at each of the 3 exposure durations. There were significant gender differences in the ECt sub 50 values for male and female rats with female rats being more sensitive to the effects of VX than males. There was significant whole blood AChE depression at the highest concentrations at each of the exposure times. The results of this study have identified several effects of VX vapor that could impact operational readiness and serve as a basis for predictions useful for military Operational Risk Management (ORM) decisions., See also ADM001736, Proceedings for the Army Science Conference (24th) held in Orlando, FL on 29 Nov-2 Dec 2005. The original document contains color images. Prepared in collaboration with Geo-Centers, Inc., Aberdeen Proving Ground, MD.
Published: 2004

16. Inhibitors of Apoptosis Affect DNA Degradation and Repair in Sulfur Mustard (HD)-Exposed Human Epidermal Keratinocytes (HEK)

Author: LINCOLN UNIV PA DEPT OF CHEMISTRY, Bhat, K. R., Dierking, E. L., Benton, B. J., Ray, R., LINCOLN UNIV PA DEPT OF CHEMISTRY, Bhat, K. R., Dierking, E. L., Benton, B. J., and Ray, R.
Abstract: In cultured HEK, we observed that HD (0.3-1.0 mM)-induced DNA damage triggers DNA repair and apoptosis, which may be interdependent. We studied the effects of a general caspase inhibitor, Z-VAD fmk (0.004 mM) and the Fas (CD95) receptor (induces apoptosis on Fas ligand binding) antibody on DNA damage and its repair in HD-exposed HEK. Both Z-VAD-fmk and the CD95 antibody reduced HD-induced DNA degradation possibly by decreasing DNA degradation or enhancing DNA repair or both. These inhibitors may be useful for modulating DNA repair and apoptosis in HD-exposed cells with potential applications in medical management of HD-induced vesication., See also ADM001523.
Published: 2003

17. Fluoride Ion Regeneration of Sarin (GB) From Minipig Tissue and Fluids Following Whole-Body GB Vapor Exposure

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Jakubowski, E. M., Mioduszewski, R. J., Manthei, J. H., Benton, B. J., Anthony, J. S., Durst, H. D., Thomson, S. A., Hulet, S. W., Edwards, J. L., Matson, K. L., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Jakubowski, E. M., Mioduszewski, R. J., Manthei, J. H., Benton, B. J., Anthony, J. S., Durst, H. D., Thomson, S. A., Hulet, S. W., Edwards, J. L., and Matson, K. L.
Abstract: A method has been developed for the analysis of a Sarin (GB) nerve agent biomarker in the tissue and biological fluids of minipigs that is very sensitive and selective. The GB biomarker was the fluoride ion regenerated GB and was found in minipig samples such as red blood cells, brain, liver, lung, and adipose tissue after whole body inhalation exposure. Regenerated GB in the samples was analyzed by GC-FPD after homogenization, addition of fluoride, pH adjustment and C18 solid-phase extraction. Samples were concentrated by injecting 2-200 uL of extract on a Tenax -TA sorbent tube along with 100 pg of decadeuterated diethyl ethyl phosphonate as the internal standard followed by thermal desorption on to the GC column. The method detection limit was 10.5 pg of agent on column. Highest levels were seen in the lungs (22.8 ng/g) and blood (18.8 ng/g) as expected after an inhalation exposure. Regenerated GB levels in red blood cells were approximately 10 times greater than in the plasma. Outside of the lungs and blood certain sections of the brain had some of the highest level of regenerated GB such as the caudate nucleus (5.46 ng/g). Other significant depots of regenerated GB included saliva (137 ng/g), nasal discharge (72 ng/g), and lachrymal discharge (186 ng/g). Limited amounts of free GB were also isolated from saliva (6.91 ng/g) and nasal discharge (0.65 ng/g)., See also ADM001523., The original document contains color images. Presented at the Joint Service Scientific Conference on Chemical and Biological Defense Research (2002) Held 19-21 Nov 2002 in Hunt Valley, MD.
Published: 2003

18. DNA Damage-Induced Apoptosis: Inhibition by Calmodulin Antagonist, Fas Receptor Antibody and Caspase Inhibitors

Author: ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Ray, R., Benton, B. J., Burke, M. E., Rockwood, T., Bhat, K. R., Anderson, D. R., Petrali, J. P., Smith, W. J., Ray, P., Rosenthal, D. S., ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Ray, R., Benton, B. J., Burke, M. E., Rockwood, T., Bhat, K. R., Anderson, D. R., Petrali, J. P., Smith, W. J., Ray, P., and Rosenthal, D. S.
Abstract: Sulfur mustard (HD, bis-(2-chloroethyl) sulfide) is a vesicant that causes DNA strand breaks and apoptosis in cultured normal human epidermal keratinocytes (NHEK). HD causes apoptosis via two independent pathways, a Ca2+/calmodulin (CaM)-mediated mitochondrial pathway and Fas receptor (CD95) pathway. We studied the effects of the exogenously added CaM antagonist W7, the CD95 antibody, the caspase-3 inhibitor Ac-DEVD-CHO, and the general caspase inhibitor Z-VAD-fmk on NHEK viability loss (Calcein AM fluorescence assay, LDH release assay) due to HD. All protected against HD. Z-VAD-fmk was the most effective. These results provide a logical approach toward developing an anti-apoptotic vesicant countermeasure., See also ADM001523. Prepared in collaboration with Walter Reed Army Institute of Research, Silver Spring, MD. and Georgetown University, Washington, D.C.
Published: 2003

19. Inhalation Toxicity of Sarin (GB) Vapor in the Gottingen Minipig: Low-Level Threshold Effects

Author: GEO-CENTERS INC ABERDEEN PROVING GROUND MD, Hulet, S. W., Miller, D. B., Crouse, C. L., Matson, K. L., Crosier, R. B., Sommerville, D. R., Benton, B. J., Forster, J. S., Manthei, J. H., Scotto, J. A., GEO-CENTERS INC ABERDEEN PROVING GROUND MD, Hulet, S. W., Miller, D. B., Crouse, C. L., Matson, K. L., Crosier, R. B., Sommerville, D. R., Benton, B. J., Forster, J. S., Manthei, J. H., and Scotto, J. A.
Abstract: The goal of these experiments was to determine the lowest sarin (GB) vapor concentration of physiological significance. Gottingen-minipigs were individually exposed to concentrations of GB vapor ranging from 0.03-2.0 mg/cu m for 60 minutes. Pupil constriction was assessed, under dim-light conditions, using an infrared light sensitive video camera and capturing high-resolution images of the eye before, during and after exposure. Pupil area was then quantified automatically off-line using a custom-designed software package. Pupil area was graphed as a function of time. The relationship between the dose-response curve (percent pupil constriction as a function of time) and vapor concentration was investigated., See also ADM001523. Presented at the Joint Service Scientific Conference on Chemical & Biological Defense Research held on 19-21 November 2002. The original document contains color images.
Published: 2003

20. Low-Level Cyclo-Sarin (GF) Vapor Exposure in Rats: Effect of Exposure Concentration and Duration on Pupil Size

Author: EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Whalley, C. E., Benton, B. J., Manthei, J. H., Way, R. A., Jakubowski Jr.,, E. M., Burnett, D. C., Gaviola, B. I., Forster, J. S., Crosier, R. B., Sommerville, D. R., EDGEWOOD CHEMICAL BIOLOGICAL CENTER ABERDEEN PROVING GROUND MD, Whalley, C. E., Benton, B. J., Manthei, J. H., Way, R. A., Jakubowski Jr.,, E. M., Burnett, D. C., Gaviola, B. I., Forster, J. S., Crosier, R. B., and Sommerville, D. R.
Abstract: The probability of cyclo-sarin (GF) vapor-induced miosis (defined as a post-exposure pupil diameter 50% or less of the pre-exposure pupil diameter) was estimated in rats exposed to various combinations of exposure concentration and duration. Groups of male and female Sprague-Dawley rats were exposed to GF vapor for a single duration (10, 60 or 240 minutes) in a whole-body dynamic chamber. Pupil diameter was measured by an infrared camem technique. For the six combinations of gender and exposure duration, the effective concentration for miosis in 50% of the exposed population (EC50) and the common probit slope were determined. Contrary to Haber's rule, ECt50 values increased with exposure duration (i.e., the Ct for 50% of the exposed population to show miosis was not constant over time). Female rats were more sensitive to GF vapor toxicity than male rats. Miosis was the only clinical sign noted following GF vapor exposure. Possible depression of blood esterase (acetylcholinesterase, butyrylcholinesterase and carboxylesterase) activities due to low-level range of GF vapor concentrations was also investigated. GF was regenerated from blood samples of vapor-exposed rats by the addition of fluoride ion at pH 4 and the samples were analyzed by GC-FPD and GC-MS. Levels of regenerated GF in the red blood cell (RBC) fraction of the samples were five to 40 times lower than in plasma. All controls were negative for regenerated GF., See also ADM001523. Proceedings of the 2002 Joint Service Scientific Conference on Chemical & Biological Defense Research, 19-21 November 2002. The original document contains color images.
Published: 2003

21. Programming the Linpack benchmark for Roadrunner

Author: Kistler, M., primary, Gunnels, J., additional, Brokenshire, D., additional, and Benton, B., additional
Published: 2009
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22. Blow-Out

Author: Wood, Benton B.
Published: 1931

23. Reversal of Saxitoxin (STX) and Tetrodotoxin (TTX) Induced Cardio-Respiratory Failure with 4-Aminopyridine (4-AP).

Author: ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Chang, F. C., Bauer, R. M., Benton, B. J., Moore, E. L., ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Chang, F. C., Bauer, R. M., Benton, B. J., and Moore, E. L.
Abstract: Reversal of STX and TTX induced cardio-respiratory failure with 4-AP was studied in urethane-anesthetized guinea pigs instrumented for the recordings of medullary respiratory activities, diaphragm EMG, ECoG, ECG, blood pressure, end-tidal CO(2), and arterial O(2)/CO2/pH. The toxin (STX or TTX) was infused at a dose rate of 0.3 ug/kg/min (i.v.) to produce a state of cardio-respiratory depression. Animals were maintained with artificial ventilation when the magnitude of diaphragm activity was reduced by 50%. Seconds after the disappearance of the diaphragm activity, the toxin infusion was terminated, and 4-AP (2 mg/kg; i.v.) was administered. The therapeutic effect of 4-AP was striking in that the toxin-induced functional blockade of the diaphragm, vascular hypotension and bradycardia could all be promptly returned to a level comparable to, and in many cases surpassing, that of control condition. The animals were typically able to breathe spontaneously within minutes after 4-AP. Despite an auspicious return of ventilatory function and cardiovascular performance, a variety of other 4-AP induced central and peripheral effects were also observed. The most notable ones are (1) a cortical excitant/arousal effect as indicated by the emergence of an 8-30 Hz EEG power spectral complex, (2) an increase in the magnitude of skeletal muscle (neck) background activities, and (3) a cardio-respiratory performance decrement noted in some animals attributable to an acid-base homeostatic imbalance which was readily reversible by sodium bicarbonate solution. Side effects at higher intravenous dose levels (viz., 4, 6, and 8 mg/kg) are of some concern in that 4-AP not only can cause muscle fasciculations, but also becomes seizurogenic and proconvulsant.
Published: 1993

24. Effect of 3,4 Diaminopyridine on Saxitoxin- and Tetrodotoxin-Induced Cardiorespiratory Depression.

Author: ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Bauer, R. M., Benton, B. J., Moore, E. L., Chang, F. C., ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD, Bauer, R. M., Benton, B. J., Moore, E. L., and Chang, F. C.
Abstract: The effect of 3,4 diaminopyridine (3,4 DAP) on saxitoxin (STX) - and tetrodotoxin (TTX)-induced cardiorespiratory depression was examined in anesthetized guinea pigs which were instrumented to record medullary respiratory neuronal activity, arterial pressure, ECG, ECoG, diaphragm EMG (DEMG), end-tidal CO(2) and arterial pH, Co(2) and O(2). Infusion of STX or TTX (0.3 ug/kg/min, IV) elicited progressive vascular hypotension, bradycardia and bradypnea leading to complete inhibition of DEMG activity. Artificial ventilation was introduced when DEMG activity was reduced by 50% due to STX or TTX. Toxin infusion was stopped upon the inhibition of DEMG activity and 3,4 DAP (8 Mg/kg, IV) was given subsequently. Arterial pressure and heart rate returned to pretoxin levels and DEMG activity reappeared rapidly following 3,4 DAP infusion. In most cases, animals resumed spontaneous breathing within minutes after 3,4 DAP. Spontaneous breathing was often sustained for several hours after a single infusion of 3,4 DAP. Uncompensated arterial acidosis was typically observed during spontaneous breathing after 3,4 DAP treatment; however, this could be corrected with sodium bicarbonate (7.5%, IV). Despite the therapeutic actions of 3,4 DAP, some side effects were identified. Adverse side effects of 3,4 DAP administration included aberrant patterns of medullary discharge. Current investigations address strategies to minimize these medullary neuronal side effects of 3,4 DAP and to potentiate its therapeutic actions.
Published: 1993

25. Cla4p, a Saccharomyces cerevisiae Cdc42p-activated kinase involved in cytokinesis, is activated at mitosis

Author: Benton, B K, primary, Tinkelenberg, A, additional, Gonzalez, I, additional, and Cross, F R, additional
Published: 1997
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26. Signal-mediated import of bacteriophage T7 RNA polymerase into the Saccharomyces cerevisiae nucleus and specific transcription of target genes

Author: Benton, B M, primary, Eng, W K, additional, Dunn, J J, additional, Studier, F W, additional, Sternglanz, R, additional, and Fisher, P A, additional
Published: 1990
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27. MISCELLANY.

Author: Bloomfield, Leonard, Becker, Roman, Jones, J. J., Wood, Benton B., Massey, B. W. A., L. P., Mason, C. P., Hausen, T. Joseph, Burwell, M. A., Schoonover, M. M., C. B. A., Meredith, Mamie, Benardete, Dolores, Zieglschmid, A. J. F., and Ericson, E. E.
Subjects: LANGUAGE & languages, HUMAN anatomy, TERMS & phrases, PHILOLOGY
Abstract: Presents news briefs on languages in the U.S. as of February 1931. Several meanings of blow-out; Application of the term ham on human anatomy; Expressions used in Boyd County.
Published: 1931

28. Isolation and characterization of constitutively active mutants of mammalian adenylyl cyclase.

Author: Hatley, M E, Benton, B K, Xu, J, Manfredi, J P, Gilman, A G, and Sunahara, R K
Abstract: A genetic screen in Saccharomyces cerevisiae identified mutations in mammalian adenylyl cyclase that activate the enzyme in the absence of G(s)alpha. Thirteen of these mutant proteins were characterized biochemically in an assay system that depends on a mixture of the two cytosolic domains (C(1) and C(2)) of mammalian adenylyl cyclases. Three mutations, I1010M, K1014N, and P1015Q located in the beta4-beta5 loop of the C(2) domain of type II adenylyl cyclase, increase enzymatic activity in the absence of activators. The K1014N mutation displays both increased maximal activity and apparent affinity for the C(1) domain of type V adenylyl cyclase in the absence of activators of the enzyme. The increased affinity of the mutant C(2) domain of adenylyl cyclase for the wild type C(1) domain was exploited to isolate a complex containing VC(1), IIC(2), and G(s)alpha-guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) in the absence of forskolin and a complex of VC(1), IIC(2), forskolin, and P-site inhibitor in the absence of G(s)alpha-GTPgammaS. The isolation of these complexes should facilitate solution of crystal structures of low activity states of adenylyl cyclase and thus determination of the mechanism of activation of the enzyme by forskolin and G(s)alpha.
Published: 2000
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29. Assessment of Dry-Aged Beef from Commercial Aging Locations Across the United States.

Author: Lancaster, Jessica M., Smart, Jaxon, Buseman, Brianna, Van Buren, Jessie B., Weber, Tanya, Insausti, Kizkitza, Nasados, James, Glaze, Benton B., Price, William, Colle, Michael, and Bass, Phillip
Subjects: BEEF, BEEF products, AIR speed, STEAK (Beef), MEAT aging, VACUUM packaging, HUMIDITY
Abstract: Dry-aging is a practice that involves storing meat at refrigerated temperatures without protective packaging. Despite the increase in dry-aged beef popularity, relatively little is known about commercial dry-aging parameters. Thus, the objectives of this study were to determine dry-aging parameters of commercial aging facilities and their influence on eating quality (acceptability, flavor, tenderness, and juiciness) of dry-aged beef from locations across the United States. Sixty-six Certified Angus Beef® brand bone-in beef strip loins (IMPS #175) were randomly assigned to ten commercial dry-aging facilities across the United States. An additional six strip loins were wet-aged for 45-days as a negative control. Strip loins were shipped overnight to aging locations where a 45-day dry aging period transpired before being returned for subsequent analysis, upon completion of aging. Objective color, pH, and water activity were measured post aging, at the time of processing. Strip loins were then fabricated, and steaks were vacuum packaged and frozen until further analysis. Intrinsic quality parameters objective color (L*, a*, b*), pH, and water activity were not different (P > 0.05) between strip loins aged 45 days by location. Cooler conditions including temperature, percent relative humidity, and air speed were different (P < 0.01) across aging locations. Pacific Northwest consumer panelists indicated a difference in overall acceptability (P < 0.01), tenderness (P = 0.01), and flavor (P < 0.01) based on aging location. Additionally, consumers detected (P < 0.01) unique dry-aging flavors for individual aging locations including cheesy and nutty attributes. Research indicates individual dry-aging facility conditions aid in producing unique dry-aged beef products according to U.S. consumers from the Pacific Northwest Region. [ABSTRACT FROM AUTHOR]
Published: 2021
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30. The Arginase and Rhodanese Activities of Certain Cell Strains after Long Cultivation in Vitro

Author: N. M. Hawkins, Wilton R. Earle, G. L. Hobbs, H. A. Kerr, Virginia J. Evans, Ellison V. Peppers, Katherine K. Sanford, M. C. Fioramonti, and Benton B. Westfall
Subjects: In Vitro Techniques, Biology, Rhodanese, Article, Amidohydrolases, Microbiology, Tissue Culture Techniques, HeLa, Mice, Tissue culture, medicine, Animals, Humans, Fibroblast, Skin, chemistry.chemical_classification, Arginase, Epidermis (botany), Cell Biology, Fibroblasts, biology.organism_classification, Molecular biology, Thiosulfate Sulfurtransferase, In vitro, Enzymes, Enzyme, medicine.anatomical_structure, chemistry, HeLa Cells
Abstract: The activities of the enzymes arginase and rhodanese were examined in homogenates of 13 mouse cell strains and 2 human cell strains after long cultivation of the cells in vitro. Three strains of mouse liver origin showed both high arginase and rhodanese activities in keeping with activities of the tissue of origin. Two strains of cells of human epithelial origin, HeLa and epidermis, were found to have high rhodanese activity but low arginase activity, the skin being almost devoid of it. Seven mouse fibroblast strains or substrains had moderate rhodanese activity and all except one of the strains had low arginase activity. Two of the fibroblast strains tested, NCTC 1745 and NCTC 2050, were derived from a single cell of a tumor appearing after injection of the high tumor producing strain NCTC 1742 into a mouse. The strain 1745 had 20 times and the strain 2050 had 400 times the arginase activity of the parent strain of cells. The findings imply a considerable biochemical variation in the three strains. Three mouse mammary carcinoma clones were devoid of arginase activity, but had considerable rhodanese activity.
Published: 1958
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31. p75, a polypeptide component of karyoskeletal protein-enriched fractions associated with transcriptionally active loci of Drosophila melanogaster polytene chromosomes

Author: Benton, B M, Berrios, S, and Fisher, P A
Abstract: A 75-kilodalton polypeptide has been identified which copurifies with karyoskeletal protein-enriched fractions prepared from Drosophila melanogaster embryos. Results of indirect immunofluorescence experiments suggest that this protein, here designated p75, is primarily associated with puffed regions of larval salivary gland polytene chromosomes. In nonpolytenized Schneider 2 tissue culture cells, p75 appeared to be localized throughout the nuclear interior during interphase. In mitotic cells, p75 was redistributed diffusely. A possible role for karyoskeletal elements in transcriptional regulation is discussed.
Published: 1988
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32. Drosophila nuclear lamin precursor Dm0 is translated from either of two developmentally regulated mRNA species apparently encoded by a single gene.

Author: Gruenbaum, Y, Landesman, Y, Drees, B, Bare, J W, Saumweber, H, Paddy, M R, Sedat, J W, Smith, D E, Benton, B M, and Fisher, P A
Abstract: A cDNA clone encoding a portion of Drosophila nuclear lamins Dm1 and Dm2 has been identified by screening a lambda-gt11 cDNA expression library using Drosophila lamin-specific monoclonal antibodies. Two different developmentally regulated mRNA species were identified by Northern blot analysis using the initial cDNA as a probe, and full-length cDNA clones, apparently corresponding to each message, have been isolated. In vitro transcription of both full-length cDNA clones in a pT7 transcription vector followed by in vitro translation in wheat germ lysate suggests that both clones encode lamin Dm0, the polypeptide precursor of lamins Dm1 and Dm2. Nucleotide sequence analyses confirm the impression that both cDNA clones code for the identical polypeptide, which is highly homologous with human lamins A and C as well as with mammalian intermediate filament proteins. The two clones differ in their 3'-untranslated regions. In situ hybridization of lamin cDNA clones to Drosophila polytene chromosomes shows only a single locus of hybridization at or near position 25F on the left arm of chromosome 2. Southern blot analyses of genomic DNA are consistent with the notion that a single or only a few highly similar genes encoding Drosophila nuclear lamin Dm0 exist in the genome.
Published: 1988
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33. The yeast immunophilin Fpr3 is a physiological substrate of the tyrosine-specific phosphoprotein phosphatase Ptp1.

Author: Wilson, L K, Benton, B M, Zhou, S, Thorner, J, and Martin, G S
Abstract: The tyrosine-specific phosphoprotein phosphatase encoded by the Saccharomyces cerevisiae PTP1 gene dephosphorylates artificial substrates in vitro, but little is known about its functions and substrates in vivo. The presence of Ptp1 resulted in dephosphorylation of multiple tyrosine-phosphorylated proteins in yeast expressing a heterologous tyrosine-specific protein kinase, indicating that Ptp1 can dephosphorylate a broad range of substrates in vivo. Correspondingly, several proteins phosphorylated at tyrosine by endogenous protein kinases exhibited a marked increase in tyrosine phosphorylation in ptp1 mutant cells. One of these phosphotyrosyl proteins (p70) was also dephosphorylated in vitro when incubated with recombinant Ptp1. p70 was purified to homogeneity; analysis of four tryptic peptides revealed that p70 is identical to the recently described FPR3 gene product, a nucleolarly localized proline rotamase of the FK506- and rapamycin-binding family. The identity of p70 with Fpr3 was confirmed in the demonstration that the abundance of tyrosine-phosphorylated p70 in ptp1 mutants was strictly correlated with the level of FPR3 expression; immobilized phosphotyrosyl Fpr3 was directly dephosphorylated by recombinant Ptp1. Site-directed mutagenesis demonstrated that the site of tyrosine phosphorylation is Tyr-184, which resides within the nucleolin-like amino-terminal domain of Fpr3. Protein kinase activities from yeast cell extracts can bind to and phosphorylate the immobilized amino-terminal domain of Fpr3 on serine, threonine, and tyrosine. Fpr3 represents the first phosphotyrosyl protein identified in S. cerevisiae that is not itself a protein kinase and is as yet the only known physiological substrate of Ptp1.
Published: 1995

34. Determination of the standard electrode potential of cobalt

Author: Westfall, Benton B. and Westfall, Benton B.
Published: 1931

35. Aquatic parameters and life history observations of the Great Basin spadefoot toad in Utah

Author: Hovingh, P, primary, Benton, B, additional, and Bornholdt, B, additional
Published: 1985
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36. Practical Physiological Chemistry . (12th ed.) P. B. Hawk, B. L. Oser, and W. H. Summerson. Philadelphia: Blakiston, 1947. Pp. xiv + 1323. (Illustrated.) $10.00.

Author: Westfall, Benton B., primary
Published: 1947
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37. The Selenium Problem in Relation to Public Health: A Preliminary Survey to Determine the Possibility of Selenium Intoxication in the Rural Population Living on Seleniferous Soil

Author: Maurice I. Smith, Benton B. Westfall, and K. W. Franke
Subjects: medicine.medical_specialty, business.industry, Public health, General Engineering, chemistry.chemical_element, chemistry, Milk products, Environmental health, Medicine, Livestock, Rural area, business, Rural population, Selenium
Published: 1936
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38. Practical Physiological Chemistry . (12th ed.) P. B. Hawk, B. L. Oser, and W. H. Summerson. Philadelphia: Blakiston, 1947. Pp. xiv + 1323. (Illustrated.) $10.00

Author: Benton B. Westfall
Subjects: Multidisciplinary, Stereochemistry, Philosophy, Physiological chemistry
Published: 1947
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39. Practical Physiological Chemistry P. B. Hawk B. L. Oser W. H. Summerson

Author: Westfall, Benton B.
Published: 1947

40. Progressive Palaeontology 2024 conference report.

Author: George H, Farrell T, Rawson JRG, Aguilar-Pedrayes I, Walters B, and Flett KE
Subjects: Humans, Paleontology
Abstract: The 20th instalment of the Progressive Palaeontology conference was held from 17th-20th of June 2024 at the University of Bristol, UK. Progressive Palaeontology gives postgraduate students experience of presenting at a conference to an audience of their peers, and the opportunity to form networks with researchers at their career stage. The conference was organised on behalf of the Palaeontological Association by Hady George, Thomas Farrell, James R. G. Rawson, Isaura Aguilar-Pedrayes, Benton Walters and Kirsten E. Flett, all of whom are postgraduate students in the Bristol Palaeobiology group. The meeting was a great success, featuring a high standard of research presentations on a wide range of topics, and inclusive and educational events hosted throughout the conference., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2024. Published by The Company of Biologists Ltd.)
Published: 2024
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41. Chromatin architecture mapping by multiplex proximity tagging.

Author: Delamarre A, Bailey B, Yavid J, Koche R, Mohibullah N, and Whitehouse I
Abstract: Chromatin plays a pivotal role in genome expression, maintenance, and replication. To better understand chromatin organization, we developed a novel proximity-tagging method which assigns unique DNA barcodes to molecules that associate in 3D space. Using this method - Proximity Copy Paste (PCP) - we mapped the connectivity of individual nucleosomes in Saccharomyces cerevisiae . We show that chromatin is predominantly organized into regularly spaced nucleosome arrays whose properties differ according to transcriptional activity. Additionally, by mapping long-range, multi-way interactions we provide evidence that metaphase chromosomes are compacted by arrayed cohesin hubs. Using single-molecule nuclease footprinting data we define distinct chromatin states within a mixed population to show that noncanonical nucleosomes are a stable feature of chromatin. PCP is a versatile method allowing the connectivity of individual molecules to be mapped at high-resolution.
Published: 2024
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42. A review of pathogen removal from municipal wastewater using advanced oxidation processes: Agricultural application, regrowth risks, and new perspectives.

Author: Oluoch B, Mandizvo T, Musazura W, Badza T, Otieno B, Ojwach S, and Odindo A
Abstract: Pathogen removal in wastewater offers a chance to recover water and nutrients for crop production, reducing environmental contamination and public health risks. However, the risk of pathogens regrowing in treated effluents can endanger public health if reused in agriculture, attracting stringent reuse standards. While advanced oxidation processes (AOPs) promise to reduce pathogens, eliminating regrowth potential in AOP-treated effluents requires further scrutiny. This review aimed to summarize the available evidence on understanding pathogen reduction and regrowth potential in AOP-treated effluents, following best practices for scoping reviews like the preferred reporting items for systematic reviews and meta-analysis (PRISMA). It covers recent pathogen studies under AOPs, current AOP investigations, the impact of AOP dosage and retention time on pathogen control, and challenges in reusing AOP-treated effluents for crop production. Additionally, it identifies areas needing improvement or complementary treatments for pathogen-free effluents with no regrowth potential. The review concludes by summarizing key findings and suggesting research areas for further exploration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)
Published: 2024
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43. Regenerating Family Member 3 Alpha Is Predictive of Mortality Following Emergent Large Vessel Occlusion.

Author: Sands M, McLouth CJ, Frank JA, Maglinger B, Millson N, Al-Kawaz MN, Pahwa S, Dornbos DL 3rd, Lukins DE, Trout AL, Stowe AM, Fraser JF, and Pennypacker KR
Subjects: Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Ischemic Stroke mortality, Ischemic Stroke blood, Prognosis, Biomarkers blood, Pancreatitis-Associated Proteins blood, Pancreatitis-Associated Proteins metabolism
Abstract: Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas with additional immunomodulatory properties. Previously, we published that REG3A expression in ischemic stroke patient systemic blood, during mechanical thrombectomy (MT), is significantly associated with inflammatory cytokines and patient function on admission. This paper, however, did not investigate post-acute death rates. Therefore, we investigated plasma REG3A protein expression, during MT, in patients (n = 141) that survived or died within the end of the follow-up after MT. Subjects who died had significantly higher systemic plasma REG3A levels at the time of MT compared to survivors ( p = 0.001). Age, sex, time from last known normal, and admission NIHSS were included as predictors to control for confounding variables and were all examined to determine their association in patient mortality. Logistic regression was used to demonstrate that higher odds of death were associated with increased REG3A levels ( p = 0.002). REG3A demonstrated acceptable discrimination (AUC (95% CI): 0.669 (0.566-0.772) in predicting mortality. The overall model with age, sex, time from last known normal, and admission NIHSS discriminated well between survivors and those who died (AUC (95% CI): 0.784 (0.703-0.864)). In conclusion, REG3A could be promising as a biomarker to prognosticate stroke outcomes and stratify high-risk groups following acute ischemic stroke.
Published: 2024
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44. Evaluating a Foundation Artificial Intelligence Model for Glaucoma Detection Using Color Fundus Photographs.

Author: Chuter B, Huynh J, Hallaj S, Walker E, Liebmann JM, Fazio MA, Girkin CA, Weinreb RN, Christopher M, and Zangwill LM
Abstract: Purpose: To evaluate RETFound, a foundation artificial intelligence model, using a diverse clinical research dataset to assess its accuracy in detecting glaucoma using optic disc photographs. The model's accuracy for glaucoma detection was evaluated across race, age, glaucoma severity, and various training cycles (epochs) and dataset sample sizes., Design: Evaluation of a diagnostic technology., Participants: The study included 9787 color fundus photographs (CFPs) from 2329 participants of diverse race (White [73.4%], Black [13.6%] and other [13%]), disease severity (21.8% mild glaucoma, 7.2% moderate or advanced glaucoma, 60.3% not glaucoma, and 10.7% unreported), and age (48.8% <60 years, 51.1% >60 years) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study. All fundus photographs were graded as "Glaucomatous" or "Non-glaucomatous.", Methods: The study employed RETFound, a self-supervised learning model, to perform binary glaucoma classification. The diagnostic accuracy of RETFound was iteratively tested across different combinations of dataset sample sizes (50-2000 optic disc photographs), training cycles (5-50), and study subpopulations stratified by severity of glaucoma, age, and race)., Main Outcome Measures: Diagnostic accuracy area under the receiver operating characteristic curve (AUC) for classifying CFP as "Glaucomatous" or "Non-glaucomatous.", Results: Performance increased with larger training datasets and more training cycles, improving from 50 training images and 5 epochs (AUC: 0.52) to 2000 training images and 50 epochs (AUC: 0.86), with reduced gain in performance from approximately 500 and 1000 training images (AUC of 0.82 and 0.83, respectively). Performance was consistent across race and age for all training size and cycle number combinations: Black (AUC = 0.87) vs. other (AUC = 0.86), and >60 years (AUC = 0.84) vs. <60 years (AUC = 0.87). Performance was significantly higher in patients with moderate to severe vs. mild glaucoma (AUC = 0.95 vs. 0.84, respectively)., Conclusions: Good RETFound performance was observed with a relatively small sample size of optic disc photographs used for fine-tuning and across differences in race and age. RETFound's ability to adapt across a range of CFP training conditions and populations suggests it is a promising tool to automate glaucoma detection in a variety of use cases., Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (© 2024 Published by Elsevier Inc. on behalf of the American Academy of Ophthalmology.)
Published: 2024
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45. Disruption of adenosine metabolism increases risk of seizure-induced death despite decreased seizure severity.

Author: Purnell B, Bhasin J, Rust B, George S, Bah K, Lu T, Fedele D, and Boison D
Subjects: Animals, Mice, Male, Pentylenetetrazole toxicity, Disease Models, Animal, Mice, Inbred C57BL, Sudden Unexpected Death in Epilepsy, Hypercapnia metabolism, Adenosine Kinase metabolism, Severity of Illness Index, Xanthines pharmacology, Adenosine metabolism, Seizures metabolism, Mice, Transgenic, Electroshock adverse effects
Abstract: Objective: Respiratory arrest plays an important role in sudden unexpected death in epilepsy (SUDEP). Adenosine is of interest in SUDEP pathophysiology due to its influence on seizures and breathing. The objective of this investigation was to examine the role of adenosine in seizure severity, seizure-induced respiratory disruption, and seizure-induced death using mouse models. Understanding adenosinergic contributions to seizure cessation and seizure-induced death may provide insights into how SUDEP can be prevented while avoiding increased seizure severity., Methods: Our approach was to examine: (1) seizure severity and seizure-induced death after 15 mA electroshock seizures and during repeated pentylenetetrazol (PTZ) administration in wild-type mice (Adk +/+ ) and transgenic mice with reduced adenosine metabolism (Adk +/- ); (2) the postictal hypercapnic ventilatory response (HCVR) in wild-type mice (the postictal HCVR could not be examined in Adk +/- mice due to their high mortality rate); and (3) the effects of adenosinergic drugs on seizure severity and seizure-induced death following maximal electroshock (MES)., Results: Adk +/- mice were more vulnerable to seizure-induced death in the 15 mA electroshock and repeated PTZ models. Despite increased mortality, Adk +/- mice had comparable seizure severity in the PTZ model and reduced seizure severity in the 15 mA electroshock model. Breathing and HCVR were suppressed by 15 mA electroshock seizures in wild-type mice. Pharmacological inhibition of adenosine metabolism decreased MES seizure severity but did not increase mortality. A 1 selective and nonselective adenosine receptor antagonists increased seizure-induced death following MES., Significance: Adenosine has opposing effects on seizure severity and seizure-induced death. On the one hand, our seizure severity data highlight the importance of adenosine in seizure suppression. On the other hand, our mortality data indicate that excessive extracellular adenosine signaling can increase the risk of seizure-induced respiratory arrest., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)
Published: 2024
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46. The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

Author: McLouth CJ, Maglinger B, Frank JA, Hazelwood HS, Harp JP, Cranford W, Pahwa S, Sheikhi L, Dornbos D 3rd, Trout AL, Stowe AM, Fraser JF, and Pennypacker KR
Subjects: Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Appalachian Region epidemiology, Treatment Outcome, Ischemic Stroke blood, Ischemic Stroke surgery, Proteomics, Thrombectomy trends, Thrombectomy methods
Abstract: Introduction: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia., Methods: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA)., Results: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS., Conclusion: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response., (© 2024. The Author(s).)
Published: 2024
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47. A Comprehensive Guide to Long-Acting Injectable Antipsychotics for Primary Care Clinicians.

Author: Krishna A, Goicochea S, Shah R, Stamper B, Harrell G, and Turner A
Subjects: Humans, Injections, Practice Guidelines as Topic, Schizophrenia drug therapy, Antipsychotic Agents administration & dosage, Delayed-Action Preparations administration & dosage, Mental Disorders drug therapy, Primary Health Care standards
Abstract: We propose a paper that provides education on commonly used long-acting injectable antipsychotics (LAIs) to improve primary care based mental health interventions in patients with severe mental illnesses (SMIs) such as schizophrenia, schizoaffective disorder, and bipolar disorders. With the expanding interface of primary care and psychiatry across all healthcare settings, it has become increasingly important for primary care clinicians to have a broader understanding of common psychiatric treatments, including LAIs. Long-acting injectable antipsychotics have been shown to be helpful in significantly improving treatment adherence, preventing disease progression, improving treatment response, decreasing readmission rates, and reducing social impairment. We discuss evidence-based indications and guidelines for use of long-acting injectable antipsychotics. We provide an overview of the treatment of SMI with LAIs, mainly focusing on the most commonly used long-acting injectable antipsychotics, advantages and disadvantages of each, along with outlining important clinical pearls for ease of practical application. Equipped with increased familiarity and understanding of these essential therapies, primary care clinicians can better facilitate early engagement with psychiatric care, promote more widespread use, and thus significantly improve the wellbeing and quality of life of patients with severe mental illness., Competing Interests: Conflict of interest: All authors declare that they have no conflicts of interests or competing interests., (© Copyright by the American Board of Family Medicine.)
Published: 2024
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48. Response surface methodology directed modeling of the biosorption of progesterone onto acid activated Moringa oleifera seed biomass: Parameters and mechanisms.

Author: Ngeno E, Ongulu R, Shikuku V, Ssentongo D, Otieno B, Ssebugere P, and Orata F
Subjects: Adsorption, Wastewater chemistry, Kinetics, Hydrogen-Ion Concentration, Endocrine Disruptors metabolism, Endocrine Disruptors chemistry, Moringa oleifera chemistry, Progesterone metabolism, Progesterone chemistry, Biomass, Water Pollutants, Chemical chemistry, Water Pollutants, Chemical metabolism, Seeds chemistry
Abstract: In this study, chemically activated fat-free powdered Moringa oleifera seed biomass (MOSB) was synthesized, characterized, and utilized as a cost-effective biosorbent for the abstraction of progesterone (PGT) hormone from synthetic wastewater. Natural PGT is a human steroid hormone from the progestogen family. Synthetic PGT is approved for the regulation of the menstrual cycle, aiding contraception, and is administered as a hormone replacement therapy in menopausal and post-menopausal women. PGT is an endocrine disrupting chemical (EDC) with negative health impacts on biota. The X-ray diffractogram (XRD), Scanning electron microscopy-Energy-dispersive X-ray spectroscopy (SEM-EDS), and Brunauer-Emmet-Teller (BET) analyses displayed a porous, amorphous biosorbent with an elemental composition of 72.5% carbon and 22.5% oxygen and a specific surface area of 210.0 m 2 g -1 . The process variables including temperature (298-338 K), pH (2-10), contact time (10-180 min), adsorbate concentration (20-500 μg L -1 ), and adsorbent dosage (0.1-2.0 g) were optimized using response surface methodology (RSM) to obtain the greatest efficacy of MOSB during biosorption of PGT. The optimum parameters for PGT biosorption onto MOSB were: 86.8 min, 500 μg L -1 adsorbate concentration, 298 K, and 0.1 g adsorbent dosage. PGT removal from aqueous solutions was pH-independent. The Langmuir isotherm best fitted the equilibrium data with maximal monolayer biosorption capacity of 135.8 μg g -1 . The biosorption rate followed the pseudo-first-order (PFO) kinetic law. The thermodynamic functions (ΔG < 0, ΔH = -9.258 kJ mol -1 and ΔS = +44.16 J mol -1 ) confirmed that the biosorption of PGT onto MOSB is a spontaneous and exothermic process with increased randomness at the adsorbent surface. The biosorption mechanism was physisorption and was devoid of electrostatic interactions. The findings from this study indicate that MOSB is an inexpensive, low-carbon, and environmentally friendly biosorbent that can effectively scavenge PGT from aqueous solutions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
Published: 2024
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49. Building large-scale registries from unstructured clinical notes using a low-resource natural language processing pipeline.

Author: Tavabi N, Pruneski J, Golchin S, Singh M, Sanborn R, Heyworth B, Landschaft A, Kimia A, and Kiapour A
Subjects: Humans, Electronic Health Records, Data Mining methods, Natural Language Processing, Registries
Abstract: Building clinical registries is an important step in clinical research and improvement of patient care quality. Natural Language Processing (NLP) methods have shown promising results in extracting valuable information from unstructured clinical notes. However, the structure and nature of clinical notes are very different from regular text that state-of-the-art NLP models are trained and tested on, and they have their own set of challenges. In this study, we propose Sentence Extractor with Keywords (SE-K), an efficient and interpretable classification approach for extracting information from clinical notes and show that it outperforms more computationally expensive methods in text classification. Following the Institutional Review Board (IRB) approval, we used SE-K and two embedding based NLP approaches (Sentence Extractor with Embeddings (SE-E) and Bidirectional Encoder Representations from Transformers (BERT)) to develop comprehensive registry of anterior cruciate ligament surgeries from 20 years of unstructured clinical data at a multi-site tertiary-care regional children's hospital. The low-resource approach (SE-K) had better performance (average AUROC of 0.94 ± 0.04) than the embedding-based approaches (SE-E: 0.93 ± 0.04 and BERT: 0.87 ± 0.09) for out of sample validation, in addition to minimum performance drop between test and out-of-sample validation. Moreover, the SE-K approach was at least six times faster (on CPU) than SE-E (on CPU) and BERT (on GPU) and provides interpretability. Our proposed approach, SE-K, can be effectively used to extract relevant variables from clinic notes to build large-scale registries, with consistently better performance compared to the more resource-intensive approaches (e.g., BERT). Such approaches can facilitate information extraction from unstructured notes for registry building, quality improvement and adverse event monitoring., Competing Interests: Declaration of competing interest No conflicts of interests relevant to the topic of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)
Published: 2024
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50. The ATCC genome portal: 3,938 authenticated microbial reference genomes.

Author: Nguyen SV, Puthuveetil NP, Petrone JR, Kirkland JL, Gaffney K, Tabron CL, Wax N, Duncan J, King S, Marlow R, Reese AL, Yarmosh DA, McConnell HH, Fernandes AS, Bagnoli J, Benton B, and Jacobs JL
Abstract: The ATCC Genome Portal (AGP, https://genomes.atcc.org/) is a database of authenticated genomes for bacteria, fungi, protists, and viruses held in ATCC's biorepository. It now includes 3,938 assemblies (253% increase) produced under ISO 9000 by ATCC. Here, we present new features and content added to the AGP for the research community., Competing Interests: The authors declare no conflict of interest.
Published: 2024
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