Risk of pancreatic ductal adenocarcinoma associated with carriage of BRCA1 and/or BRCA2 mutation: A systematic review and meta-analysis.

Germline BRCA1/2 mutations lead to malfunction of DNA damage repair pathways and predispose to pancreatic ductal adenocarcinoma (PDAC). The aim of this study is to synthesise the available research on this topic. Four studies reporting risk ratio (RR) were included in the final meta-analysis to minimise misrepresenting our results by combining separate risk estimates. Our meta-analysis revealed a statistically significant increased risk of PDAC in BRCA carriers overall (RR: 2.65, 95% confidence interval: 1.43-4.91, p = 0.002).

Kinetic consequences of the endogenous ligand to molybdenum in the DMSO reductase family: a case study with periplasmic nitrate reductase.

The molybdopterin enzyme family catalyzes a variety of substrates and plays a critical role in the cycling of carbon, nitrogen, arsenic, and selenium. The dimethyl sulfoxide reductase (DMSOR) subfamily is the most diverse family of molybdopterin enzymes and the members of this family catalyze a myriad of reactions that are important in microbial life processes. Enzymes in the DMSOR family can transform multiple substrates; however, quantitative information about the substrate preference is sparse, and, more importantly, the reasons for the substrate selectivity are not clear. Molybdenum coordination has long been proposed to impact the catalytic activity of the enzyme. Specifically, the molybdenum-coordinating residue may tune substrate preference. As such, molybdopterin enzyme periplasmic nitrate reductase (Nap) is utilized as a vehicle to understand the substrate preference and delineate the kinetic underpinning of the differences imposed by exchanging the molybdenum ligands. To this end, NapA from Campylobacter jejuni has been heterologously overexpressed, and a series of variants, where the molybdenum coordinating cysteine has been replaced with another amino acid, has been produced. The kinetic properties of these variants are discussed and compared with those of the native enzyme, providing quantitative information to understand the function of the molybdenum-coordinating residue.

Youth Perceptions of Sport-Confidence.

ABSTRACT: Zuk, EF, Maksymiw, K, Evanovich, J, McGarry, JE, Root, HJ, and Distefano, LJ. Youth perceptions in sport-confidence. J Strength Cond Res 35(11): 3232-3235, 2021-Sport-confidence is an important construct that is often missed during physical activity interventions in youth. Male and female children might display differences in sport-confidence that influences their activity levels. The purpose of this study is to assess any association between sport-confidence and gender in elementary school and middle-school children. All 286 children {(boys [ES: n = 71, age = 8±1 years; MS: n = 63, 11±1 years]; girls [ES: n = 67, 7±1 years; MS: n = 85, 11±1 years])} completed the Physical Literacy Assessment for Youth-Self Questionnaire. Separate chi-square tests of the association were used to evaluate the association between gender and sport-confidence among elementary (grades K-4) and middle-school (grades 5-8) children because of varying injury and participation rates for these groups, for each relevant question with a significance set at p ≤ 0.05. For elementary school children, there were no significant associations between genders and sport-confidence (p > 0.05). In middle-school children, there were significant associations detected for learning new skills (ϕ = 0.12; p = 0.031), perception of skill (ϕ = 0.12; p = 0.054), confidence in activity (ϕ = 0.17; p = 0.035), and being the best in the class (ϕ = 0.15; p = 0.048) between genders and sport-confidence. For all results, boys displayed more sport-confidence than girls. Education for key stakeholders about the importance of including sport-confidence in physical activity interventions is integral in promoting life-long activity, specifically in middle-school girls.

The Relationship Between Physical Activity and Executive Functions Among Youth in Low-Income Urban Schools in the Northeast and Southwest United States.

The purpose of this study was to examine if physical activity is related to greater executive functions among youth in poverty. Executive functions (cognitive flexibility, inhibition, and working memory) and physical activity were measured in participants (N = 149) in the fifth to eighth grade from three schools located in high-poverty districts. Pearson correlations revealed a statistically significant correlation between physical activity and cognitive flexibility (r = .18, p < .05). Hierarchical multiple regressions revealed that physical activity significantly improved prediction for cognitive flexibility, R2 = .09, F(6, 142) = 2.26, p = .041, adjusted R2 = .05, above sex, maturity, and school district. A two-way multivariate analysis of covariance revealed statistically significant differences in working memory in more active youth compared with less active but no statistically significant differences in cognitive flexibility or inhibition (p < .05). Greater physical activity is associated with greater working memory among youth in poverty.

Respiratory Selenite Reductase from Bacillus selenitireducens Strain MLS10.

The putative respiratory selenite [Se(IV)] reductase (Srr) from Bacillus selenitireducens MLS10 has been identified through a polyphasic approach involving genomics, proteomics, and enzymology. Nondenaturing gel assays were used to identify Srr in cell fractions, and the active band was shown to contain a single protein of 80 kDa. The protein was identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a homolog of the catalytic subunit of polysulfide reductase (PsrA). It was found to be encoded as part of an operon that contains six genes that we designated srrE, srrA, srrB, srrC, srrD, and srrF SrrA is the catalytic subunit (80 kDa), with a twin-arginine translocation (TAT) leader sequence indicative of a periplasmic protein and one putative 4Fe-4S binding site. SrrB is a small subunit (17 kDa) with four putative 4Fe-4S binding sites, SrrC (43 kDa) is an anchoring subunit, and SrrD (24 kDa) is a chaperon protein. Both SrrE (38 kDa) and SrrF (45 kDa) were annotated as rhodanese domain-containing proteins. Phylogenetic analysis revealed that SrrA belonged to the PsrA/PhsA clade but that it did not define a distinct subgroup, based on the putative homologs that were subsequently identified from other known selenite-respiring bacteria (e.g., Desulfurispirillum indicum and Pyrobaculum aerophilum). The enzyme appeared to be specific for Se(IV), showing no activity with selenate, arsenate, or thiosulfate, with a Km of 145 ± 53 µM, a Vmax of 23 ± 2.5 µM min-1, and a kcat of 23 ± 2.68 s-1 These results further our understanding of the mechanisms of selenium biotransformation and its biogeochemical cycle.IMPORTANCE Selenium is an essential element for life, with Se(IV) reduction a key step in its biogeochemical cycle. This report identifies for the first time a dissimilatory Se(IV) reductase, Srr, from a known selenite-respiring bacterium, the haloalkalophilic Bacillus selenitireducens strain MLS10. The work extends the versatility of the complex iron-sulfur molybdoenzyme (CISM) superfamily in electron transfer involving chalcogen substrates with different redox potentials. Further, it underscores the importance of biochemical and enzymological approaches in establishing the functionality of these enzymes.

Upon further analysis, neither cytochrome c554 from Nitrosomonas europaea nor its F156A variant display NO reductase activity, though both proteins bind nitric oxide reversibly.

A re-investigation of the interaction with NO of the small tetraheme protein cytochrome c554 (C554) from Nitrosomonas europaea has shown that the 5-coordinate heme II of the two- or four-electron-reduced protein will nitrosylate reversibly. The process is first order in C554, first order in NO, and second-order overall. The rate constant for NO binding to the heme is 3000 ± 140 M-1s-1, while that for dissociation is 0.034 ± 0.009 s-1; the degree of protein reduction does not appear to significantly influence the nitrosylation rate. In contrast to a previous report (Upadhyay AK, et al. J Am Chem Soc 128:4330, 2006), this study found no evidence of C554-catalyzed NO reduction, either with [Formula: see text] or with [Formula: see text] Some sub-stoichiometric oxidation of the lowest potential heme IV was detected when [Formula: see text] was exposed to an excess of NO, but this is believed to arise from partial intramolecular electron transfer that generates {Fe(NO)}8 at heme II. The vacant heme II coordination site of C554 is crowded by three non-bonding hydrophobic amino acids. After replacing one of these (Phe156) with the smaller alanine, the nitrosylation rate for F156A2- and F156A4- was about 400× faster than for the wild type, though the rate of the reverse denitrosylation process was almost unchanged. Unlike in the wild-type C554, the 6-coordinate low-spin hemes of F156A4- oxidized over the course of several minutes after exposure to NO. Concomitant formation of N2O could explain this heme oxidation, though alternative explanations are equally plausible given the available data.

Utility of CT colonography and/or PET-CT preoperatively in obstructing left-sided colorectal cancers - a systematic review.

PURPOSE: 15-20% of patients present with near obstructing left-sided colorectal cancer. CT colonography (CTC) or PET-CT has been used to detect synchronous lesions, which may alter preoperative planning of colonic resection. We aim to synthesize the usefulness of CT colonography and/or PET-CT in detecting synchronous proximal colon carcinomas in patients who have undergone an incomplete colonoscopy due to a stenosing or obstructing distal colorectal cancer. METHODOLOGY: A systematic review was performed by searching the databases up to December 2021. Data collected included demographics of the study population, rate of detection of synchronous carcinomas and impact on management of detection of synchronous carcinomas. RESULTS: A total of 22 studies were included: 17 studies focused on CTC, 3 on PET-CT, and 2 integrated PET-CT with CTC; 2855 patients were included; 53% of patients were male, and 47% were female. All studies reported detection of synchronous proximal colorectal carcinomas using CTC, PET-CT or CTC, and PET-CT combined. CTC detected synchronous carcinomas in 0.2-12.2% of patients. PET-CT was useful in detecting synchronous carcinomas in 4.05-23% of patients. Integrated PET-CT and CTC detected synchronous carcinomas in 2-15% of patients. The surgical plan was changed in 2.4-14.3% of patients after the use of CTC. One PET-CT study reported a change in management in 13.5%. No complication was reported by the use of CTC. CONCLUSION: CTC is an effective and useful adjunct to colonoscopy in assessing the proximal colon when colonoscopy fails to do so. However, more evidence is needed with the use of PET-CT for this patient population.

Positive Impacts of a Sport Intervention on Male Students of Color and School Climate.

A positive school climate is strongly associated with enhanced student outcomes. With the disengagement of Black and Latinx youth living in poverty being at an all-time high, participation in sport-based youth development (SBYD) programs may enhance school climate, while capitalizing on existing interests. Purpose: The purpose of this study was to examine the impact of a SBYD intervention on male students of color and school climate. Method: Using a mixed-methods quasi-experimental design, 32 male students of color (11 Black, 13 Latinx, 8 two or more races) participated in an SBYD intervention, twice a week for a total of 20 weeks (Ages 10-14, M = 11.46). School climate data were gathered at the beginning and the end of the school year. Student, teacher, and administrator focus groups and interviews were also conducted at the end of the year. Results: A statistically significant interaction was found between students who participated in the intervention and those who did not participate in the intervention, on school climate measures F(1,74) = 15.00, p < .01, partial η2 = .17. Overall school climate scores were statistically significantly greater in the intervention group (F(1,74) = 19.22, p < .01, partial η2 = .20) at the end of the year. Focus group data also revealed themes of improved school connectedness, peer support, the acquisition of social/civic skills, and school engagement. Conclusions: A SBYD intervention may be a viable strategy to engage disconnected students and increase school climate perceptions, particularly among male students of color living in poverty.

Interaction of nitric oxide with catalase: structural and kinetic analysis.

We present the structures of bovine catalase in its native form and complexed with ammonia and nitric oxide, obtained by X-ray crystallography. Using the NO generator 1-(N,N-diethylamino)diazen-1-ium-1,2-diolate, we were able to generate sufficiently high NO concentrations within the catalase crystals that substantial occupation was observed despite a high dissociation rate. Nitric oxide seems to be slightly bent from the heme normal that may indicate some iron(II) character in the formally ferric catalase. Microspectrophotometric investigations inline with the synchrotron X-ray beam reveal photoreduction of the central heme iron. In the cases of the native and ammonia-complexed catalase, reduction is accompanied by a relaxation phase. This is likely not the case for the catalase NO complex. The kinetics of binding of NO to catalase were investigated using NO photolyzed from N,N'-bis(carboxymethyl)-N,N'-dinitroso-p-phenylenediamine using an assay that combines catalase with myoglobin binding kinetics. The off rate is 1.5 s(-1). Implications for catalase function are discussed.

Enzymatic interconversion of ammonia and nitrite: the right tool for the job.

Hydroxylamine oxidoreductase (HAO) from Nitrosomonas europaea normally catalyzes oxidation of NH(2)OH to NO(2)(-). This paper reports experiments in which HAO was thermodynamically poised to catalyze reduction of NO(2)(-) to NH(4)(+). HAO was found to catalyze the reduction of NO(2)(-) by methyl viologen monocation radical (MV(red)), displaying a hyperbolic dependence on NO(2)(-) concentration, with a k(cat1) of 6.8 ± 0.3 s(-1) and a K(m1) of 7.6 ± 0.9 mM. HAO also catalyzed the reduction of NH(2)OH by MV(red), with a hyperbolic dependence on NH(2)OH concentration, and a k(cat2) of 245 ± 3 s(-1) and a K(m2) of 6.8 ± 0.2 mM (k(cat1) and k(cat2) reflect the maximum number of electrons transferred from MV(red) per second). We had previously demonstrated that HAO catalyzes the reduction of NO by MV(red) to yield first NH(2)OH and then NH(4)(+). Thus, overall, HAO is seen to act like a cytochrome c nitrite reductase, which catalyzes the six-electron reduction of NO(2)(-) to NH(4)(+) by MV(red). In the presence of Ru(NH(3))(2+) (Ru(II)) and Ru(NH(3))(3+) (Ru(III)) at ratios exceeding 200:1, HAO exhibited no detectable Ru(II)-NO(2)(-) oxidoreductase activity, though such activity is thermodynamically favored. On the other hand, HAO could still catalyze the oxidation of NH(2)OH to NO by Ru(III) under these conditions. The oxidative process exhibited a hyperbolic dependence on NH(2)OH concentration, with a k(cat3) of 98 ± 3 s(-1) and a K(m3) of 5.2 ± 0.8 µM. Finally, HAO was found not to catalyze the disproportionation of NH(2)OH, despite the thermodynamic favorability of such a process, and the apparent opportunity presented by the HAO structure. Mechanisms are proposed to explain all the kinetic data.

Validation of the Professional Identity and Values Scale Among an Athletic Trainer Population.

CONTEXT: Forming a professional identity is a process by which an individual achieves an awareness of his or her own self-concept in the context of the profession. Identity in relation to an individual's profession includes the ability to articulate one's role as a professional and professional philosophy. Professional identity has been studied extensively in other fields, but currently no professional identity scales have been validated within the athletic training profession. OBJECTIVE: To validate the Professional Identity and Values Scale (PIVS) among an athletic trainer population. DESIGN: Cross-sectional study. SETTING: Web-based questionnaire. PATIENTS OR OTHER PARTICIPANTS: Athletic trainers employed in National Collegiate Athletic Association Division I, II, III, or National Association of Intercollegiate Athletics colleges or universities (n = 299, 56.5% female, 43.5% male). The average age of the participants was 33.6 ± 8.3 years, and they had 10.3 ± 7.6 years of experience. MAIN OUTCOME MEASURE(S): Participants were asked to complete a demographic questionnaire and the 32-item PIVS. The variables included demographics and the PIVS (Professional Orientation and Values subscale [18 items] and the Professional Development subscale [14 items]). RESULTS: Exploratory factor analysis reduced the survey from 32 to 20 items and revealed 6 factors. Three factors emerged from the Professional Development subscale and emphasized professional insecurities during the early career stages, the importance of mentors during the intermediate stages, and self-confidence and awareness during the later stages of professional development. An additional 3 factors emerged from the Professional Orientation and Values subscale: (1) patient care and advocacy, (2) professional engagement and collaboration, and (3) personal wellness and values. A Cronbach α of 0.80 indicated good internal consistency. CONCLUSIONS: A modified PIVS is a valid and reliable measure of professional identity among athletic trainers employed in the collegiate setting.

Multilevel Examination of Job Satisfaction and Career Intentions of Collegiate Athletic Trainers: A Quantitative Approach.

CONTEXT: Recent employment data from collegiate athletic training settings have demonstrated departure trends among men and women. These trends have been hypothesized to be related to work-life balance. However, work-life balance is only 1 aspect of a myriad of factors. Due to the complex nature of the work-life interface, a multilevel examination is needed to better understand the precipitators of departure. OBJECTIVE: To quantitatively examine factors that may influence collegiate athletic trainers' (ATs') job satisfaction and career intentions via a multilevel examination of the work-life interface. DESIGN: Cross-sectional study. SETTING: Web-based questionnaire. PATIENTS OR OTHER PARTICIPANTS: Athletic trainers employed in National Collegiate Athletic Association Division I, II, or III or National Association of Intercollegiate Athletics colleges or universities (N = 299: 56.5% female, 43.5% male). The average age of participants was 33.6 ± 8.3 years, and their average experience was 10.3 ± 7.6 years. DATA COLLECTION AND ANALYSIS: Participants responded to an online questionnaire consisting of demographic questions, 9 Likert-scale surveys, and open-ended questions. Job-satisfaction Scores (JSSs) and intention-to-leave scores (ITLSs) served as the dependent variables and factors from individual, organizational, and sociocultural levels were the independent variables. Hierarchical regression analysis was run to determine the predictability of factors. RESULTS: No sex differences in ITLS or JSS were found in our sample. Independent variables explained 68.5% of the variance in JSS and 28.8% of the variance in ITLS. Additions of factor levels increased the percentage of explained variance in both scores. CONCLUSIONS: A combination of individual-, organizational-, and sociocultural-level factors was able to best predict JSS and ITLS among collegiate ATs.

Molecular cloning, expression and biochemical characterization of periplasmic nitrate reductase from Campylobacter jejuni.

Campylobacter jejuni, a human gastrointestinal pathogen, uses nitrate for growth under microaerophilic conditions using periplasmic nitrate reductase (Nap). The catalytic subunit, NapA, contains two prosthetic groups, an iron sulfur cluster and a molybdenum cofactor. Here we describe the cloning, expression, purification, and Michaelis-Menten kinetics (kcat of 5.91 ± 0.18 s-1 and a KM (nitrate) of 3.40 ± 0.44 µM) in solution using methyl viologen as an electron donor. The data suggest that the high affinity of NapA for nitrate could support growth of C. jejuni on nitrate in the gastrointestinal tract. Site-directed mutagenesis was used and the codon for the molybdenum coordinating cysteine residue has been exchanged for serine. The resulting variant NapA is 4-fold less active than the native enzyme confirming the importance of this residue. The properties of the C. jejuni enzyme reported here represent the first isolation and characterization of an epsilonproteobacterial NapA. Therefore, the fundamental knowledge of Nap has been expanded.

Techniques for investigating hydroxylamine disproportionation by hydroxylamine oxidoreductases.

Hydroxylamine, an important intermediate in ammonia oxidation by ammonia oxidizing bacteria (AOB), is inherently unstable with respect to disproportionation. The process is slow in neutral solutions, but could potentially be catalyzed by enzymes such as the hydroxylamine oxidoreductases, which normally catalyze the oxidation of ammonia to nitrite in the AOB. Disproportionation could be physiologically important to some AOB under microaerobic conditions, and could also confound in vitro analyses if it occurs and is not taken into consideration. This chapter presents methods for detecting ammonia, nitric oxide, nitrite, nitrous oxide, and isotopically labeled dinitrogen, which are the most thermodynamically favored products of hydroxylamine disproportionation.