Census 2010 Demographic Profile: Jefferson County

This demographic profile describes characteristics of the local and state population based on results from the 2010 Census. The decennial census is an official enumeration, or count, of all residents on April 1st of the census year. The results of the census provide us with information about basic demographic characteristics of the population, including age, race, ethnicity, household composition, housing occupancy, and housing tenure

Management of primary hypothyroidism: statement by the British Thyroid Association Executive Committee

The management of primary hypothyroidism with levothyroxine (L-T4) is simple, effective and safe, and most patients report improved well-being on initiation of treatment. However, a proportion of individuals continue to suffer with symptoms despite achieving adequate biochemical correction. The management of such individuals has been the subject of controversy and of considerable public interest. The American Thyroid Association (ATA) and the European Thyroid Association (ETA) have recently published guidelines on the diagnosis and management of hypothyroidism. These guidelines have been based on extensive reviews of the medical literature and include sections on the role of combination therapy with L-T4 and liothyronine (L-T3) in individuals who are persistently dissatisfied with L-T4 therapy. This position statement by the British Thyroid Association (BTA) summarises the key points in these guidelines and makes recommendations on the management of primary hypothyroidism based on the current literature, review of the published positions of the ETA and ATA, and in line with best principles of good medical practice. The statement is endorsed by the Association of Clinical Biochemistry, (ACB), British Thyroid Foundation, (BTF), Royal College of Physicians (RCP) and Society for Endocrinology (SFE)

Relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort.

OBJECTIVES: To describe the characteristics of children and adults with incident type 1 diabetes in contemporary, multiethnic UK, focusing on differences between the islet autoantibody negative and positive. DESIGN: Observational cohort study. SETTING: 146 mainly secondary care centres across England and Wales. PARTICIPANTS: 3312 people aged ≥5 years were recruited within 6 months of a clinical diagnosis of type 1 diabetes via the National Institute for Health Research Clinical Research Network. 3021 were of white European ethnicity and 291 (9%) were non-white. There was a small male predominance (57%). Young people <17 years comprised 59%. MAIN OUTCOME MEASURES: Autoantibody status and characteristics at presentation. RESULTS: The majority presented with classical osmotic symptoms, weight loss and fatigue. Ketoacidosis was common (42%), especially in adults, and irrespective of ethnicity. 35% were overweight or obese. Of the 1778 participants who donated a blood sample, 85% were positive for one or more autoantibodies against glutamate decarboxylase, islet antigen-2 and zinc transporter 8. Presenting symptoms were similar in the autoantibody-positive and autoantibody-negative participants, as was the frequency of ketoacidosis (43%vs40%, P=0.3). Autoantibody positivity was less common with increasing age (P=0.0001), in males compared with females (82%vs90%, P<0.0001) and in people of non-white compared with white ethnicity (73%vs86%, P<0.0001). Body mass index was higher in autoantibody-negative adults than autoantibody-positive adults (median, IQR 25.5, 23.1-29.2vs23.9, 21.4-26.7 kg/m2; P=0.0001). Autoantibody-negative participants were more likely to have a parent with diabetes (28%vs16%, P<0.0001) and less likely to have another autoimmune disease (4%vs8%, P=0.01). CONCLUSIONS: Most people assigned a diagnosis of type 1 diabetes presented with classical clinical features and islet autoantibodies. Although indistinguishable at an individual level, autoantibody-negative participants as a group demonstrated features more typically associated with other diabetes subtypes. TRIAL REGISTRATION NUMBER: ISRCTN66496918; Pre-results

Topical steroid therapy induces pro-tolerogenic changes in Langerhans cells in human skin

We have investigated the efficacy of conditioning skin Langerhans cells (LCs) with agents to promote tolerance and reduce inflammation, with the goal of improving the outcomes of antigen-specific immunotherapy. Topical treatments were assessed ex vivo, using excised human breast skin maintained in organ bath cultures, and in vivo in healthy volunteers by analysing skin biopsies and epidermal blister roof samples. Following topical treatment with a corticosteroid, TNF-α levels were reduced in skin biopsy studies and blister fluid samples. Blister fluid concentrations of MCP-1, MIP-1α, MIP-1β and IP-10 were also reduced, while preserving levels of IL-1α, IL-6, IL-8 and IL-10. Steroid pre-treatment of the skin reduced the ability of LCs to induce proliferation, whilst supernatants showed an increase in the IL-10/IFN-γ ratio. Phenotypic changes following topical steroid treatment were also observed, including reduced expression of CD83 and CD86 in blister derived LCs, but preservation of the tolerogenic signalling molecules ILT3 and PD-1. Reduced expression of HLA-DR, CD80 and CD86 were also apparent in LCs derived from excised human skin. Topical therapy with a vitamin D analogue (calcipotriol) and steroid, calcipotriol alone or Vitamin A elicited no significant changes in the parameters studied. These experiments suggest that pre-conditioning the skin with topical corticosteroid can modulate LCs by blunting their pro-inflammatory signals and potentially enhancing tolerance. We suggest that such modulation prior to antigen specific immunotherapy might provide an inexpensive and safe adjunct to current approaches to treat autoimmune diseases

Longitudinal characterization of autoantibodies to the thyrotropin receptor (TRAb) during alemtuzumab therapy; evidence that TRAb may precede thyroid dysfunction by many years.

BACKGROUND Thyroid autoimmunity, especially Graves’ disease or hypothyroidism with positive autoantibodies (TRAb) to the thyrotropin receptor (TSHR), occurs in 30-40% of patients with relapsing multiple sclerosis (MS) following treatment with alemtuzumab (ALTZ). ALTZ therapy therefore provides a unique opportunity to study the evolution of TRAb prior to clinical presentation. TRAb can stimulate (TSAb), block (TBAb) or not affect (“neutral”: TNAb) the TSHR function, causing hyperthyroidism, hypothyroidism or euthyroidism, respectively. METHODS We conducted a longitudinal retrospective analysis of TRAb bioactivity over a period of 9 years in 45 MS patients receiving ALTZ using available stored serum; 31 developed thyroid dysfunction (TD) and 14 remained euthyroid despite being followed for a minimum of 5 years (NO-TD). The presence of TRAb was evaluated at standardized time points: A) pre-ALTZ, B) latest time available post-ALTZ and before TD onset, C) post-ALTZ during/after TD onset. Serum TRAb were detected by published in-house assays (ihTRAb): flow cytometry (FC) detecting any TSHR-binding TRAb and luciferase bioassays (LB) detecting TSAb/TBAb bioactivity. Purified IgGs were used to verify TSAb/TBAb in selected hypothyroid cases. Standard clinical automated measurements of TRAb (autTRAb), anti-thyroid peroxidase autoantibodies (TPOAb), thyroid stimulating hormone, free-thyroxine and free-triiodothyronine were also collected. RESULTS Pre-ALTZ, combined ihTRAb (positive with FC and/or LB), but not autTRAb, were present in 5/16 (31.2%) TD versus 0/14 (0%) NO-TD (p=0.017). Detectable ihTRAb preceded TD development in 9/28 (32.1%) and by a median of 1.2 years (range 28 days – 7.3 years). Combination testing of ihTRAb and TPOAb at baseline predicted 20% of subsequent cases of hyperthyroidism and 83% of hypothyroidism. CONCLUSIONS We present evidence that TRAb measured with custom-made assays can be detected prior to any change in thyroid function in up to a third of cases of ALTZ-related TD. Furthermore, The presence of ihTRAb prior to ALTZ treatment was strongly predictive of subsequent TD. Our findings suggest that a period of affinity maturation of TRAb may precede clinical disease onset in some cases. Combined testing of TPOAb and ihTRAb may increase our ability to predict those who will develop thyroid dysfunction post ALTZ

The second wave of the Controlled Antenatal Thyroid Screening (CATS II) study: the cognitive assessment protocol

Background Children whose mothers had low thyroid hormone levels during pregnancy have been reported to have decreased cognitive function. The reported research is part of the follow-on study of the Controlled Antenatal Thyroid Screening Study (CATS I), a randomised controlled trial which investigated the impact of treated vs. untreated low thyroid hormone level in women during pregnancy with the primary outcome being the child’s IQ at age 3. No significant differences in IQ were found between the treated and untreated groups. These children are now aged between 7 and 10 years and aspects of their cognitive functioning including their IQ are being reassessed as part of CATS II. Methods/Design Cognitive assessments generate an IQ score and further tests administered will investigate long term memory function and motor coordination. The aim is to complete the assessments with 40% of the children born to mothers either in the treated or untreated low thyroid hormone groups (n = 120 per group). Also children born to mothers who had normal thyroid functioning during CATS I are being assessed for the first time (n = 240) to provide a comparison. Assessments are conducted either in the research facility or the participant’s home. Discussion The study is designed to assess the cognitive functioning of children born to mothers with low thyroid hormone levels and normal thyroid functioning during pregnancy. This is the largest study of its type and also is distinguishable in its longitudinal design. The research has the potential to have a significant impact on public health policy in the UK; universal screening of thyroid hormone levels in pregnancy may be the recommendation. Keywords: Hypothyroidism; Pregnancy; Child; Intelligence; IQ; Cognition; Motor coordination; Long term memory; Thyroid functio

Is there a role for natural desiccated thyroid in the treatment of levothyroxine unresponsive hypothyroidism? Results from a consecutive case series

From Wiley via Jisc Publications RouterHistory: received 2021-08-10, rev-recd 2021-09-19, accepted 2021-10-06, pub-electronic 2021-11-20Article version: VoRPublication status: PublishedAbstract: Introduction: Some levothyroxine unresponsive individuals with hypothyroidism are prescribed a natural desiccated thyroid (NDT) preparation such as Armour Thyroid ® or ERFA Thyroid ® . These contain a mixture of levothyroxine and liothyronine in a fixed ratio. We evaluated the response to NDT in individuals at a single endocrine centre in terms of how the change from levothyroxine to NDT impacted on their lives in relation to quality of life (QOL) and thyroid symptoms. Methods: The ThyPRO39 (thyroid symptomatology) and EQ‐5D‐5L‐related QoL/EQ5D5L (generic QOL) questionnaires were administered to 31 consecutive patients who had been initiated on NDT, before initiating treatment/6 months later. Results: There were 28 women and 3 men. The dose range of NDT was 60‐180 mg daily. Age range was 26‐77 years with length of time since diagnosis with hypothyroidism ranging from 2 to 40 years. One person discontinued the NDT because of lack of response; two because of cardiac symptoms. EQ‐5D‐5L utility increased from a mean (SD) of 0.214 (0.338) at baseline, to 0.606 (0.248) after 6 months; corresponding to a difference of 0.392 (95% CI 0.241‐0.542), t = 6.82, P < .001. EQ‐VAS scores increased from 33.4 (17.2) to 71.1 (17.5), a difference of 37.7 (95% CI 25.2‐50.2), t = −4.9, P < .001. ThyPRO scores showed consistent fall across all domains with the composite QoL‐impact Score improving from 68.3 (95% CI 60.9‐75.7) to 25.2 (95% CI 18.7‐31.7), a difference of 43.1 (95% CI 33‐53.2) (t = 5.6, P < .001). Conclusion: Significant symptomatic benefit and improvement in QOL was experienced by people with a history of levothyroxine unresponsive hypothyroidism treated with NDT, suggesting the need for further evaluation of NDT in this context

Association of elevated urinary miR-126, miR-155, and miR-29b with diabetic kidney disease

Effective diabetic kidney disease (DKD) biomarkers remain elusive, and urinary miRNAs represent a potential source of novel noninvasive disease sentinels. We profiled 754 miRNAs in pooled urine samples from DKD patients (n = 20), detecting significantly increased miR-126, miR-155, and miR-29b compared with controls (n = 20). These results were confirmed in an independent cohort of 89 DKD patients, 62 diabetic patients without DKD, and 41 controls: miR-126 (2.8-fold increase; P < 0.0001), miR-155 (1.8-fold increase; P < 0.001), and miR-29b (4.6-fold increase; P = 0.024). Combined receiver operating characteristic curve analysis resulted in an area under the curve of 0.8. A relative quantification threshold equivalent to 80% sensitivity for each miRNA gave a positive signal for 48% of DKD patients compared with 3.6% of diabetic patients without DKD. Laser-capture microdissection of renal biopsy specimens, followed by quantitative RT-PCR, detected miR-155 in glomeruli and proximal and distal tubules, whereas miR-126 and miR-29b were most abundant in glomerular extracts. Subsequent experiments showed miR-126 and miR-29b enrichment in glomerular endothelial cells (GEnCs) compared with podocytes, proximal tubular epithelial cells, and fibroblasts. Significantly increased miR-126 and miR-29b were detected in GEnC conditioned medium in response to tumor necrosis factor-α and transforming growth factor-β1, respectively. Our data reveal an altered urinary miRNA profile associated with DKD and link these variations to miRNA release from GEnCs

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al