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Article ; Online: Vitamin D Abnormalities

Craig Sheedy / Meng Xu / Ben Saville / Jill Simmons

Journal of Diabetes Mellitus, Vol 04, Iss 04, Pp 324-

More Common in US Children with T1D than in Healthy Children

2014 Volume 333

Abstract: ... bone mineral density, which may be due in part to low 25-hydroxyvitamin D levels. Vitamin D levels are influenced ... by sunlight exposure and thus display geographical variation. We hypothesize that the prevalence of 25-hydroxyvitamin D ... associated with 25-hydroxyvitamin D levels. Methods: Medical records of patients with T1D being followed ...

Abstract	Background: Pediatric patients with type 1 diabetes (T1D) have increased risk for low bone mineral density, which may be due in part to low 25-hydroxyvitamin D levels. Vitamin D levels are influenced by sunlight exposure and thus display geographical variation. We hypothesize that the prevalence of 25-hydroxyvitamin D deficiency (<20 ng/mL) and insufficiency (20 - 29 ng/mL) in children with T1D living in the United States is higher than in healthy children and that diabetes duration, HbA1c, and insulin dose/kg are inversely associated with 25-hydroxyvitamin D levels. Methods: Medical records of patients with T1D being followed in Tennessee were reviewed for demographics, medical information, and 25-hydroxyvitamin D levels during the previous 2 years. Control subjects were obtained from a de-identified database of healthy pediatric subjects living in a similar geographical area. Chi squared tests and multivariable linear regression were performed. Results: Children and adolescents with T1D (n = 276; median age 14 years) have a significantly higher percentage of vitamin D deficiency and insufficiency compared with healthy pediatric controls (n = 100; median age 11.2 years) (68% versus 44%; p < 0.001). The median 25-hydroxyvitamin D level is 24 ng/mL versus 31 ng/mL, respectively. After adjusting for age, race, gender, UV light exposure, BMI, and multivitamin supplementation, children and adolescents with T1D have a serum 25-hydroxyvitamin D level 6.7 ng/mL lower than the control population [CI(4.11, 9.21), p < 0.0001]. Within the T1D population, there is no clear association between diabetes duration, HbA1c, or insulin dose/kg and 25-hydroxyvitamin D levels. Conclusions: There is an increased prevalence of 25-hydroxyvitamin D deficiency and insufficiency in US. children with T1D compared with geographically similar children without diabetes. Further research is needed to determine whether decreased serum 25-hydroxyvitamin D can be alleviated via dietary or behavioral modifications in this population.
Keywords	Vitamin D Deficiency ; Vitamin D Insufficiency ; 25-Hydroxyvitamin D ; Diabetes Mellitus Type 1 ; Pediatric ; Nutritional diseases. Deficiency diseases ; RC620-627 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2014-10-01T00:00:00Z
Publisher	Scientific Research Publishing
Document type	Article ; Online
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Article ; Online: Prevalence of 25-hydroxyvitamin D deficiency in child and adolescent patients undergoing hematopoietic cell transplantation compared to a healthy population.

Simmons, Jill / Sheedy, Craig / Lee, Haerin / Koh, Shannon / Alvarez, Joann / Koyama, Tatsuki / Friedman, Debra

Pediatric blood & cancer

2013 Volume 60, Issue 12, Page(s) 2025–2030

Abstract: ... at risk for low bone mineral density, which may due, in part, to low 25-hydroxyvitamin D levels ... Procedure: We compared the serum 25-hydroxyvitamin D status of 22 pediatric HCT patients with 100 healthy pediatric ... controls. We determined the prevalence of and risk factors for 25-hydroxyvitamin D insufficiency and ...

Abstract	Background: Pediatric patients undergoing allogeneic hematopoietic cell transplant (HCT) are at risk for low bone mineral density, which may due, in part, to low 25-hydroxyvitamin D levels. Procedure: We compared the serum 25-hydroxyvitamin D status of 22 pediatric HCT patients with 100 healthy pediatric controls. We determined the prevalence of and risk factors for 25-hydroxyvitamin D insufficiency and deficiency. Results: Serum 25-hydroxyvitamin D levels were lower in the pediatric HCT patients at time of transplant than healthy pediatric controls (median 19.5 ng/ml vs. 31.0 ng/ml, P < 0.001). Of HCT patients, 27% were 25-hydroxyvitamin D deficient (<15 ng/dl) and 68% insufficient (15-29 ng/dl), compared with 4% and 40%, respectively, of healthy pediatric controls (P < 0.001). In multivariable analysis, treatment with HCT, decreased ambient ultraviolet light exposure, non-Caucasian race, and older age were associated with decreased serum 25-hydroxyvitamin D levels. No association was found between 25-hydroxyvitamin D levels and gender, body mass index, dietary vitamin D intake, or patient-reported vitamin D supplementation. Few patients in either group reported sunscreen use, vitamin D supplementation, or recommended dietary vitamin D intake. Conclusions: At time of transplant, pediatric HCT patients frequently have 25-hydroxyvitamin D insufficiency/deficiency, and this occurs more commonly than in the healthy pediatric population. HCT patients rarely follow recommended guidelines to take supplemental vitamin D, consume the Recommended Daily Allowance for vitamin D, or regularly use sunscreen. Further studies are needed to determine whether vitamin D insufficiency/deficiency persists long term in HCT patients and requires dietary and behavioral interventions.
MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Diet ; Dietary Supplements ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Prevalence ; Sunlight ; Surveys and Questionnaires ; Vitamin D/analogs & derivatives ; Vitamin D/blood ; Vitamin D Deficiency/blood ; Vitamin D Deficiency/epidemiology
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H)
Language	English
Publishing date	2013-12
Publishing country	United States
Document type	Comparative Study ; Journal Article
ZDB-ID	2131448-2
ISSN	1545-5017 ; 1545-5009
ISSN (online)	1545-5017
ISSN	1545-5009
DOI	10.1002/pbc.24684
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Article: Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome.

Sheedy, John R / Wettenhall, Richard E H / Scanlon, Denis / Gooley, Paul R / Lewis, Donald P / McGregor, Neil / Stapleton, David I / Butt, Henry L / DE Meirleir, Kenny L

In vivo (Athens, Greece)

2009 Volume 23, Issue 4, Page(s) 621–628

Abstract: ... similar to those of patients presented with D-lactic acidosis. A significant increase of Gram positive ... is presented in this report. The viable count of D-lactic acid producing Enterococcus and ... negative Escherichia coli. Further, both E. faecalis and S. sanguinis secrete more D-lactic acid than E ...

Abstract	Patients with chronic fatigue syndrome (CFS) are affected by symptoms of cognitive dysfunction and neurological impairment, the cause of which has yet to be elucidated. However, these symptoms are strikingly similar to those of patients presented with D-lactic acidosis. A significant increase of Gram positive facultative anaerobic faecal microorganisms in 108 CFS patients as compared to 177 control subjects (p<0.01) is presented in this report. The viable count of D-lactic acid producing Enterococcus and Streptococcus spp. in the faecal samples from the CFS group (3.5 x 10(7) cfu/L and 9.8 x 10(7) cfu/L respectively) were significantly higher than those for the control group (5.0 x 10(6) cfu/L and 8.9 x 10(4) cfu/L respectively). Analysis of exometabolic profiles of Enterococcus faecalis and Streptococcus sanguinis, representatives of Enterococcus and Streptococcus spp. respectively, by NMR and HPLC showed that these organisms produced significantly more lactic acid (p<0.01) from (13)C-labeled glucose, than the Gram negative Escherichia coli. Further, both E. faecalis and S. sanguinis secrete more D-lactic acid than E. coli. This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS. Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.
MeSH term(s)	Carbon Isotopes ; Chromatography, High Pressure Liquid ; Enterococcus faecalis/metabolism ; Escherichia coli/metabolism ; Fatigue Syndrome, Chronic/metabolism ; Fatigue Syndrome, Chronic/microbiology ; Feces/microbiology ; Gram-Negative Anaerobic Bacteria/metabolism ; Humans ; Intestines/microbiology ; Lactic Acid/metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Retrospective Studies ; Streptococcus sanguis/metabolism
Chemical Substances	Carbon Isotopes ; Lactic Acid (33X04XA5AT)
Language	English
Publishing date	2009-07
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
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Article: The enduring legacy of Glenn Fry, Ph.D.

Sheedy, J E

Journal of the American Optometric Association

1996 Volume 67, Issue 7, Page(s) 375–376

MeSH term(s)	History, 20th Century ; Humans ; Ohio ; Optometry/education ; Optometry/history
Language	English
Publishing date	1996-07
Publishing country	United States
Document type	Biography ; Editorial ; Historical Article ; Portrait
ZDB-ID	410349-x
ISSN	0003-0244
ISSN	0003-0244
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Article ; Online: Analysis of hairless corepressor mutants to characterize molecular cooperation with the vitamin D receptor in promoting the mammalian hair cycle.

Hsieh, Jui-Cheng / Slater, Stephanie A / Whitfield, G Kerr / Dawson, Jamie L / Hsieh, Grace / Sheedy, Craig / Haussler, Carol A / Haussler, Mark R

Journal of cellular biochemistry

2010 Volume 110, Issue 3, Page(s) 671–686

Abstract: The mammalian hair cycle requires both the vitamin D receptor (VDR) and the hairless (Hr ...

Abstract	The mammalian hair cycle requires both the vitamin D receptor (VDR) and the hairless (Hr) corepressor, each of which is expressed in the hair follicle. Hr interacts directly with VDR to repress VDR-targeted transcription. Herein, we further map the VDR-interaction domain to regions in the C-terminal half of Hr that contain two LXXLL-like pairs of motifs known to mediate contact of Hr with the RAR-related orphan receptor alpha and with the thyroid hormone receptor, respectively. Site-directed mutagenesis indicates that all four hydrophobic motifs are required for VDR transrepression by Hr. Point mutation of rat Hr at conserved residues corresponding to natural mutants causing alopecia in mice (G985W and a C-terminal deletion DeltaAK) and in humans (P95S, C422Y, E611G, R640Q, C642G, N988S, D1030N, A1040T, V1074M, and V1154D), as well as alteration of residues in the C-terminal Jumonji C domain implicated in histone demethylation activity (C1025G/E1027G and H1143G) revealed that all Hr mutants retained VDR association, and that transrepressor activity was selectively abrogated in C642G, G985W, N988S, D1030N, V1074M, H1143G, and V1154D. Four of these latter Hr mutants (C642G, N988S, D1030N, and V1154D) were found to associate normally with histone deacetylase-3. Finally, we identified three regions of human VDR necessary for association with Hr, namely residues 109-111, 134-201, and 202-303. It is concluded that Hr and VDR interact via multiple protein-protein interfaces, with Hr recruiting histone deacetylases and possibly itself catalyzing histone demethylation to effect chromatin remodeling and repress the transcription of VDR target genes that control the hair cycle.
MeSH term(s)	Alopecia/genetics ; Alopecia/metabolism ; Animals ; Conserved Sequence ; Hair/physiology ; Histone Deacetylases/metabolism ; Humans ; Immunoprecipitation ; Mutagenesis, Site-Directed ; Mutation ; Rats ; Receptors, Calcitriol/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism
Chemical Substances	HR protein, human ; Receptors, Calcitriol ; Transcription Factors ; hr protein, rat ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2010-05-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	392402-6
ISSN	1097-4644 ; 0730-2312
ISSN (online)	1097-4644
ISSN	0730-2312
DOI	10.1002/jcb.22578
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Article: Newly Diagnosed Hypokalemic Periodic Paralysis Triggered by COVID-19.

Schulte, Kelly / Sheedy, Maxwell / Feustel, Kavanya / Scherbak, Dmitriy

Cureus

2023 Volume 15, Issue 10, Page(s) e47906

Abstract: Hypokalemic periodic paralysis (HypoPP) is a rare genetic disorder characterized by low potassium levels and episodic periods of muscle weakness. HypoPP has previously been attributed to numerous viral infections; however, cases related to coronavirus ... ...

Abstract	Hypokalemic periodic paralysis (HypoPP) is a rare genetic disorder characterized by low potassium levels and episodic periods of muscle weakness. HypoPP has previously been attributed to numerous viral infections; however, cases related to coronavirus disease 2019 (COVID-19) are extremely limited. The current case is thus unique and involves a healthy 23-year-old male who presented to the emergency department after several uncharacteristic falls and three days of upper and lower extremity weakness. Initial labs revealed a potassium level of 1.1 mmol/L as well as being COVID-19 positive. Potassium supplementation helped stabilize his levels and relieved all of his symptoms. Based on an extensive clinical workup and significant family history of the mother and maternal grandmother with weakness in the setting of hypokalemia, a diagnosis of HypoPP was made. Upon discharge, he was placed on potassium-sparing diuretics to help prevent further symptom relapse and advised to complete genetic testing. With the high likelihood of the virus being endemic for years to come, clinicians should remember to consider HypoPP with patients with muscle weakness, especially in patients with concurrent COVID-19 infection, to minimize unnecessary workup and prevent potentially life-threatening symptoms of hypokalemia.
Language	English
Publishing date	2023-10-29
Publishing country	United States
Document type	Case Reports
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.47906
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Article ; Online: Substance Use Screening, Brief Intervention, and Referral to Treatment in Multiple Settings: Evaluation of a National Initiative.

Hunt, Dana / Fischer, Leigh / Sheedy, Kaitlin / Karon, Samantha

The Journal of adolescent health : official publication of the Society for Adolescent Medicine

2022 Volume 71, Issue 4S, Page(s) S9–S14

Abstract: Purpose: This study evaluated the implementation and outcomes of a multisite initiative to identify and intervene in adolescent substance use across the many settings where youth interact. This paper focuses on the implementation and intermediate ... ...

Abstract	Purpose: This study evaluated the implementation and outcomes of a multisite initiative to identify and intervene in adolescent substance use across the many settings where youth interact. This paper focuses on the implementation and intermediate outcomes of the initiative, while others in the supplement address impact and ultimate outcomes. Methods: A mixed-methods cross-grantee evaluation was conducted from 2014 to 2019 among 56 recipients of funding from the Conrad N. Hilton Foundation to implement screening, brief intervention, and referral to treatment (SBIRT) across more than 1,266 youth-facing settings. Qualitative and quantitative data were collected from grantees on a quarterly basis, as well as from grantee proposals, progress reports, monthly grantee monitoring calls, and survey findings. Results: Grantees reported increased capacity to provide SBIRT to youth across various settings: pediatric and primary care practices, community behavioral health organizations, juvenile justice programs, schools, and community-based organizations. Collectively, grantees screened 141,230 youth for substance use, 12,272 received a brief intervention, and 2,212 were referred to treatment. As part of the initiative, grantees provided SBIRT training to over 37,000 nursing and social work students, medical residents, addiction medicine fellows, and others. Implementation challenges included fitting screening into the workflow of primary care settings, confidentiality and consent in schools, reimbursement, and lack of specialist providers to refer to for substance use disorder treatment. Intermediate outcomes collected include total numbers of youth screened, received a brief intervention, and/or referred to more intensive treatment based on their screening scores. Conclusions: Research on SBIRT in adolescents has been limited to date despite positive outcomes reported in adults. This mixed-methods evaluation of an initiative to expand SBIRT implementation demonstrates feasibility of expanding access to substance use screening and intervention for youth across multiple settings and identifies challenges of implementation that differ somewhat based on settings.
MeSH term(s)	Adolescent ; Adult ; Child ; Crisis Intervention ; Humans ; Mass Screening/methods ; Referral and Consultation ; Research ; Substance-Related Disorders/prevention & control ; Substance-Related Disorders/therapy
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1063374-1
ISSN	1879-1972 ; 1054-139X
ISSN (online)	1879-1972
ISSN	1054-139X
DOI	10.1016/j.jadohealth.2022.03.002
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Article: A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase.

Vu, Jonathan T / Tavasoli, Katherine U / Mandjikian, Lori / Sheedy, Connor J / Bacal, Julien / Morrissey, Meghan A / Richardson, Chris D / Gardner, Brooke M

bioRxiv : the preprint server for biology

2024

Abstract: Peroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel ... ...

Abstract	Peroxisomes are membrane-bound organelles harboring metabolic enzymes. In humans, peroxisomes are required for normal development, yet the genes regulating peroxisome function remain unclear. We performed a genome-wide CRISPRi screen to identify novel factors involved in peroxisomal homeostasis. We found that inhibition of RNF146, an E3 ligase activated by poly(ADP-ribose), reduced the import of proteins into peroxisomes. RNF146-mediated loss of peroxisome import depended on the stabilization and activity of the poly(ADP-ribose) polymerase tankyrase, which binds the peroxisomal membrane protein PEX14. We propose that RNF146 and tankyrase regulate peroxisome import efficiency by PARsylation of proteins at the peroxisome membrane. Interestingly, we found that the loss of peroxisomes increased tankyrase and RNF146-dependent degradation of non-peroxisomal substrates, including the beta-catenin destruction complex component AXIN1, which was sufficient to alter the amplitude of beta-catenin transcription. Together, these observations not only suggest previously undescribed roles for RNF146 in peroxisomal regulation, but also a novel role in bridging peroxisome function with Wnt/beta-catenin signaling during development.
Language	English
Publishing date	2024-02-04
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.02.578667
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Article ; Online: The Evidence Base for Prevention of Infectious Bovine Keratoconjunctivitis Through Vaccination.

Maier, Gabriele / O'Connor, Annette M / Sheedy, David

The Veterinary clinics of North America. Food animal practice

2021 Volume 37, Issue 2, Page(s) 341–353

Abstract: Pili and cytotoxins are important virulence factors and antigens for Moraxella spp. Local and systemic immunity may play a role in the body's response to infectious bovine keratoconjunctivitis (IBK). No evidence exists that eliminating the carrier state ... ...

Abstract	Pili and cytotoxins are important virulence factors and antigens for Moraxella spp. Local and systemic immunity may play a role in the body's response to infectious bovine keratoconjunctivitis (IBK). No evidence exists that eliminating the carrier state for IBK is possible or beneficial. Evidence for efficacious transfer of passive immunity from dams to calves is conflicting. Autogenous vaccines and commercial vaccines for putative pathogens for IBK have not yet shown efficacy in blinded randomized field trials. Study design features, such as randomization, blinding, diagnostic criteria, and use of a placebo, reduce the risk of bias in vaccine studies for IBK.
MeSH term(s)	Animals ; Bacterial Vaccines/administration & dosage ; Bacterial Vaccines/immunology ; Cattle ; Cattle Diseases/prevention & control ; Keratoconjunctivitis, Infectious/immunology ; Keratoconjunctivitis, Infectious/prevention & control ; Vaccination/veterinary
Chemical Substances	Bacterial Vaccines
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	286086-7
ISSN	1558-4240 ; 0749-0720
ISSN (online)	1558-4240
ISSN	0749-0720
DOI	10.1016/j.cvfa.2021.03.009
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Article ; Online: Temperature and Season Influence Phagocytosis By B1 Lymphocytes in the Mojave Desert Tortoise.

Slama, Summer L / Williams, Grace S / Painter, Mariah N / Sheedy, Maxwell D / Sandmeier, Franziska C

Integrative and comparative biology

2022

Abstract: Lymphocytes are usually interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells (B1 lymphocytes) have innate immune functions, including phagocytosis, in the peripheral blood of ectothermic vertebrates. We ... ...

Abstract	Lymphocytes are usually interpreted as functioning in adaptive immunity despite evidence that large proportions of these cells (B1 lymphocytes) have innate immune functions, including phagocytosis, in the peripheral blood of ectothermic vertebrates. We used a recently optimized assay to assess environmental influences on phagocytic activity of lymphocytes isolated from the Mojave desert tortoise (Gopherus agassizii). Previous studies suggest that lymphocytes in this species are associated with reduced pathogen loads, especially in cooler climates, and that lymphocyte numbers fluctuate seasonally. Thus, we evaluated thermal dependence of phagocytic activity in vitro and across seasons. While B1 lymphocytes appeared to be cold-adapted and always increased phagocytosis at cool temperatures, we also found evidence of thermal acclimation. Tortoises upregulated these lymphocytes during cooler seasons in the fall as their preferred body temperatures dropped, and phagocytosis also increased in efficiency during this same time. Like many other ectothermic species, populations of desert tortoises are in decline, in part due to a cold-adapted pathogen that causes chronic respiratory disease. Future studies, similarly focused on the function of B1 lymphocytes, could serve to uncover new patterns in thermal acclimation of immune functions and disease ecology across taxa of ectothermic vertebrates.
Language	English
Publishing date	2022-05-10
Publishing country	England
Document type	Journal Article
ZDB-ID	2159110-6
ISSN	1557-7023 ; 1540-7063
ISSN (online)	1557-7023
ISSN	1540-7063
DOI	10.1093/icb/icac025
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