An accurate diagnostic test is an essential aspect of successfully monitoring and managing wildlife diseases. Lymphoproliferative Disease Virus (LPDV) is an avian retrovirus that was first identified ...in domestic turkeys in Europe and was first reported in a Wild Turkey (Meleagris gallopavo) in the United States in 2009. It has since been found to be widely distributed throughout North America. The majority of studies have utilized bone marrow and PCR primers targeting a 413-nucleotide sequence of the gag gene of the provirus to detect infection. While prior studies have evaluated the viability of other tissues for LPDV detection (whole blood, spleen, liver, cloacal swabs) none to date have studied differences in detection rates when utilizing different genomic regions of the provirus. This study examined the effectiveness of another section of the provirus, a 335-nucleotide sequence starting in the U3 region of the LTR (Long Terminal Repeat) and extending into the Matrix of the gag region (henceforth LTR), for detecting LPDV. Bone marrow samples from hunter-harvested Wild Turkeys (n = 925) were tested for LPDV with the gag gene and a subset (n = 417) including both those testing positive and those where LPDV was not detected was re-tested with LTR. The positive percent agreement (PPA) was 97.1% (68 of 70 gag positive samples tested positive with LTR) while the negative percent agreement (NPA) was only 68.0% (236 of 347 gag negative samples tested negative with LTR). Cohen's Kappa (κ = 0.402, Z = 10.26, p<0.0001) and the McNemar test (OR = 55.5, p<0.0001) indicated weak agreement between the two gene regions. We found that in Iowa Wild Turkeys use of the LTR region identified LPDV in many samples in which we failed to detect LPDV using the gag region and that LTR may be more appropriate for LPDV surveillance and monitoring. However, neither region of the provirus resulted in perfect detection and additional work is necessary to determine if LTR is more reliable in other geographic regions where LPDV occurs.
Sport psychology (SP), is often dominated by hegemonic viewpoints, and has historically lacked multiculturalism and awareness of intersectional oppression and marginalized identities, resulting in ...feelings of alienation for Black, Indigenous and people of color (BIPOC) practitioners. Literature from Association for Applied Sport Psychology (AASP) recommends mentorship as a way to foster professional growth and well-being. However, recommendations are often vague concerning the obstacles to success, systemic racism, sexism, and other forms of oppression that affect young professionals. By combining the specific demands of SP with critical race theory, feminist and womanist mentorship practices, and intersectionality, we outline a model of mentorship that aims to foster well-being and retention for BIPOC professionals. Specific recommendations include (1) directly naming obstacles related to systemic oppression; (2) fostering a sense of mutual care, trust, and refuge between mentor and mentee; and (3) avoiding exploitation and advocating for mentee success and thriving. Questions to be considered are (1) whether same-identity mentorship is necessary for a successful mentor-mentee relationship; and (2) how to work within a neoliberal university or sporting system.
Lay summary: Mentorship is essential to becoming a competent and certified sport psychology professional. Research has noted that most sport psychologists are white and male, and we use various theories to examine how mentorship practices can improve so that more minority and female practitioners can join and thrive in the profession.
IMPLICATIONS FOR PRACTICE
In order to transform the field, mid-level and experienced sport psychology practitioners who have the capacity should provide caring, critical, and collaborative mentorship to BIPOC practitioners.
Practitioners who serve as mentors should deliberately discuss the racism, misogyny, and other obstacles that exist in sports and academia.
Mentors should borrow from feminist, womanist, CRT, and intersectionality scholars to create liberatory non-hierarchal relationships that foster institutional change.
Systematic Review of the Human Milk Microbiota Fitzstevens, John L.; Smith, Kelsey C.; Hagadorn, James I. ...
Nutrition in Clinical Practice,
June 2017, Letnik:
32, Številka:
3
Book Review, Journal Article
Recenzirano
Human milk–associated microbes are among the first to colonize the infant gut and may help to shape both short- and long-term infant health outcomes. We performed a systematic review to characterize ...the microbiota of human milk. Relevant primary studies were identified through a comprehensive search of PubMed (January 1, 1964, to June 31, 2015). Included studies were conducted among healthy mothers, were written in English, identified bacteria in human milk, used culture-independent methods, and reported primary results at the genus level. Twelve studies satisfied inclusion criteria. All varied in geographic location and human milk collection/storage/analytic methods. Streptococcus was identified in human milk samples in 11 studies (91.6%) and Staphylococcus in 10 (83.3%); both were predominant genera in 6 (50%). Eight of the 12 studies used conventional ribosomal RNA (rRNA) polymerase chain reaction (PCR), of which 7 (87.5%) identified Streptococcus and 6 (80%) identified Staphylococcus as present. Of these 8 studies, 2 (25%) identified Streptococcus and Staphylococcus as predominant genera. Four of the 12 studies used next-generation sequencing (NGS), all of which identified Streptococcus and Staphylococcus as present and predominant genera. Relative to conventional rRNA PCR, NGS is a more sensitive method to identify/quantify bacterial genera in human milk, suggesting the predominance of Streptococcus and Staphylococcus may be underestimated in studies using older methods. These genera, Streptococcus and Staphylococcus, may be universally predominant in human milk, regardless of differences in geographic location or analytic methods. Primary studies designed to evaluate the effect of these 2 genera on short- and long-term infant outcomes are warranted.
Autosomal dominant mutations in leucine rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson’s disease (PD). Despite the presence of multiple domains, the kinase activity of ...LRRK2 is thought to represent the primary function of the protein. Alterations in LRRK2 kinase activity are thought to underlie the pathogenesis of its PD-linked mutations; however, many questions regarding basic aspects of LRRK2 function remain unclear, including the cellular mechanisms of LRRK2 regulation and the importance of its unique distribution within the cell. Here, we demonstrate for the first time that the subcellular localization of wild-type LRRK2 is associated with changes in four distinct biochemical properties likely crucial for LRRK2 function. Our data demonstrate for the first time that the wild-type LRRK2 dimer possesses greater kinase activity than its more abundant monomeric counterpart. Importantly, we show that this activated form of LRRK2 is substantially enriched at the membrane of cells expressing endogenous or exogenous LRRK2, and that the membrane-associated fraction of LRRK2 likewise possesses greater kinase activity than cytosolic LRRK2. In addition, membrane-associated LRRK2 binds GTP more efficiently than cytosolic LRRK2 but demonstrates a lower degree of phosphorylation. Our observations suggest that multiple events, including altered protein−protein interactions and post-translational modifications, contribute to the regulation of LRRK2 function, through modulation of membrane association and complex assembly. These findings may have implications for the sites of LRRK2 function within the cell, the identification and localization of bona fide LRRK2 substrates, and efforts to design small molecule inhibitors of LRRK2.
Inborn errors of immunity manifesting as atopic disorders Vaseghi-Shanjani, Maryam; Smith, Kelsey L.; Sara, Rahnuma J. ...
Journal of allergy and clinical immunology,
November 2021, 2021-11-00, 20211101, Letnik:
148, Številka:
5
Journal Article
Recenzirano
Inborn errors of immunity are traditionally best known for enhancing susceptibility to infections. However, allergic inflammation, among other types of immune dysregulation, occurs frequently in ...patients with inborn errors of immunity. As such, the term primary atopic disorders (PADs) was recently coined to describe the group of heritable monogenic allergic disorders. It is becoming increasingly important for clinicians to recognize that allergic diseases such as food allergy, atopic dermatitis, and allergic asthma are expressions of misdirected immunity, and in patients who present with severe, early-onset, or coexisting allergic conditions, these can be indications of an underlying PAD. Identifying monogenic allergic disease through next-generation sequencing can dramatically improve outcomes by allowing the use of precision-based therapy targeting the patient’s underlying molecular defect. It is therefore imperative that clinicians recognize PADs to be able to provide informed therapeutic options and improve patient outcomes. Here, we summarize the clinical features commonly seen with each of the currently known PADs, identify clinical warning signs that warrant assessment for PADs, and lastly, discuss the benefits of timely diagnosis and management of these conditions.
Fibroblast growth factor 23 (FGF-23) is a hormone that increases the rate of urinary excretion of phosphate and inhibits renal production of 1,25-dihydroxyvitamin D, thus helping to mitigate ...hyperphosphatemia in patients with kidney disease. Hyperphosphatemia and low 1,25-dihydroxyvitamin D levels are associated with mortality among patients with chronic kidney disease, but the effect of the level of FGF-23 on mortality is unknown.
We examined mortality according to serum phosphate levels in a prospective cohort of 10,044 patients who were beginning hemodialysis treatment and then analyzed FGF-23 levels and mortality in a nested case-control sample of 200 subjects who died and 200 who survived during the first year of hemodialysis treatment. We hypothesized that increased FGF-23 levels at the initiation of hemodialysis would be associated with increased mortality.
Serum phosphate levels in the highest quartile (>5.5 mg per deciliter 1.8 mmol per liter) were associated with a 20% increase in the multivariable adjusted risk of death, as compared with normal levels (3.5 to 4.5 mg per deciliter 1.1 to 1.4 mmol per liter) (hazard ratio, 1.2; 95% confidence interval CI, 1.1 to 1.4). Median C-terminal FGF-23 (cFGF-23) levels were significantly higher in case subjects than in controls (2260 vs. 1406 reference units per milliliter, P<0.001). Multivariable adjusted analyses showed that increasing FGF-23 levels were associated with a monotonically increasing risk of death when examined either on a continuous scale (odds ratio per unit increase in log-transformed cFGF-23 values, 1.8; 95% CI, 1.4 to 2.4) or in quartiles, with quartile 1 as the reference category (odds ratio for quartile 2, 1.6 95% CI, 0.8 to 3.3; for quartile 3, 4.5 95% CI, 2.2 to 9.4; and for quartile 4, 5.7 95% CI, 2.6 to 12.6).
Increased FGF-23 levels appear to be independently associated with mortality among patients who are beginning hemodialysis treatment. Future studies might investigate whether FGF-23 is a potential biomarker that can be used to guide strategies for the management of phosphorus balance in patients with chronic kidney disease.
Seizures are a common manifestation of paraneoplastic neurologic syndromes. The objective of this study was to describe the seizure characteristics and outcomes in patients with high-risk ...paraneoplastic autoantibodies (>70% cancer association) and to determine factors associated with ongoing seizures.
Patients from 2000 to 2020 with seizures and high-risk paraneoplastic autoantibodies were retrospectively identified. Factors associated with ongoing seizures at last follow-up were evaluated.
Sixty patients were identified (34 males, median age at presentation = 52 years). ANNA1-IgG (Hu; n = 24, 39%), Ma2-IgG (n = 14, 23%), and CRMP5-IgG (CV2; n = 11, 18%) were the most common underlying antibodies. Seizures were the initial presenting symptom in 26 (43%), and malignancy was present in 38 (63%). Seizures persisted for >1 month in 83%, and 60% had ongoing seizures, with almost all patients (55/60, 92%) still being on antiseizure medications at last follow-up a median of 25 months after seizure onset. Ongoing seizures at last follow-up were associated with Ma2-IgG or ANNA1-IgG compared to other antibodies (p = .04), highest seizure frequency being at least daily (p = .0002), seizures on electroencephalogram (EEG; p = .03), and imaging evidence of limbic encephalitis (LE; p = .03). Death occurred in 48% throughout the course of follow-up, with a higher mortality in patients with LE than in those without LE (p = .04). Of 31 surviving patients at last follow-up, 55% continued to have intermittent seizures.
Seizures in the setting of high-risk paraneoplastic antibodies are frequently resistant to treatment. Ongoing seizures are associated with ANNA1-IgG and Ma2-IgG, high seizure frequency, and EEG and imaging abnormalities. Although a subset of patients may respond to immunotherapy and achieve seizure freedom, poor outcomes are frequently encountered. Death was more common among patients with LE.
Children with sickle cell disease (SCD) are at risk for working memory deficits due to multiple disease processes. We assessed working memory abilities and related functions in 32 school-age children ...with SCD and 85 matched comparison children using Baddeley's working memory model as a framework. Children with SCD performed worse than controls for working memory, central executive function, and processing/rehearsal speed. Central executive function was found to mediate the relationship between SCD status and working memory, but processing speed did not. Cognitive remediation strategies that focus on central executive processes may be important for remediating working memory deficits in SCD.
Over a third of older adults in the U.S. experience significant vision loss, which decreases independence and is a biomarker of decreased health span. As the global aging population is expanding, it ...is imperative to uncover strategies to increase health span and reduce the economic burden of this age-related disease. While there are some treatments available for age-related vision loss, such as surgical removal of cataracts, many causes of vision loss, such as dry age-related macular degeneration (AMD), remain poorly understood and no treatments are currently available. Therefore, it is necessary to better understand the factors that contribute to disease progression for age-related vision loss and to uncover methods for disease prevention. One such factor is the effect of diet on ocular diseases. There are many reviews regarding micronutrients and their effect on eye health. Here, we discuss the impact of dietary patterns on the incidence and progression of age-related eye diseases, namely AMD, cataracts, diabetic retinopathy, and glaucoma. Then, we focus on the specific role of dietary carbohydrates, first by outlining the physiological effects of carbohydrates on the body and then how these changes translate into eye and age-related ocular diseases. Finally, we discuss future directions of nutrition research as it relates to aging and vision loss, with a discussion of caloric restriction, intermittent fasting, drug interventions, and emerging randomized clinical trials. This is a rich field with the capacity to improve life quality for millions of people so they may live with clear vision for longer and avoid the high cost of vision-saving surgeries.
Impulsive choice may play an important role in serious health-related decisions, like addiction tendencies. Thus, there is merit in exploring interventions that reduce impulsive choice. ...Delay-exposure training involves extended experience with delayed reinforcement. Following training, delay-exposed rats make fewer impulsive choices than control rats. The reducing effects of delay exposure training on impulsive choice have been replicated in male rats seven times. For the first time, this study evaluated the effects of delay exposure training in female rats. Thirty-six rats were randomly assigned to either delay-exposure or immediacy-exposure training. Then, rats underwent two impulsive choice assessments in which they chose between one immediate pellet or three delayed pellets. In the first assessment, delays increased within-sessions, across trial blocks from 0, 8, 16, to 32 s. In the second assessment, delays to the larger reward increased between-sessions, from 8, 16, 32, to 4 s. Unlike findings with male rats, delay-exposure training produced a reduction in impulsive choice only in the initial five sessions in female rats. Possible reasons for the lack of lasting effect in female rats are discussed and future research directions are identified.
•Effects of delay-exposure training were assessed for the first time in female rats with two impulsive choice assessments.•Delay-exposure training produced only a temporary reduction in impulsive choice in female rats.•The difference in impulsive choice across groups did not maintain after the first five sessions of the assessment.•Future directions and possible explanations for the lack of lasting effect are discussed.
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