Genetic landscape of Gullah African Americans.

OBJECTIVES: Gullah African Americans are descendants of formerly enslaved Africans living in the Sea Islands along the coast of the southeastern U.S., from North Carolina to Florida. Their relatively high numbers and geographic isolation were conducive to the development and preservation of a unique culture that retains deep African features. Although historical evidence supports a West-Central African ancestry for the Gullah, linguistic and cultural evidence of a connection to Sierra Leone has led to the suggestion of this country/region as their ancestral home. This study sought to elucidate the genetic structure and ancestry of the Gullah. MATERIALS AND METHODS: We leveraged whole-genome genotype data from Gullah, African Americans from Jackson, Mississippi, African populations from Sierra Leone, and population reference panels from Africa and Europe to infer population structure, ancestry proportions, and global estimates of admixture. RESULTS: Relative to non-Gullah African Americans from the Southeast US, the Gullah exhibited higher mean African ancestry, lower European admixture, a similarly small Native American contribution, and increased male-biased European admixture. A slightly tighter bottleneck in the Gullah 13 generations ago suggests a largely shared demographic history with non-Gullah African Americans. Despite a slightly higher relatedness to populations from Sierra Leone, our data demonstrate that the Gullah are genetically related to many West African populations. DISCUSSION: This study confirms that subtle differences in African American population structure exist at finer regional levels. Such observations can help to inform medical genetics research in African Americans, and guide the interpretation of genetic data used by African Americans seeking to explore ancestral identities.

Hobnail variant of papillary thyroid carcinoma: a systematic review and meta-analysis.

OBJECTIVE: The hobnail variant of papillary thyroid carcinoma (HVPTC) has emerged as a rare and aggressive variant of papillary thyroid carcinoma (PTC). We aim to determine the prevalence and clinicopathologic factors of HVPTC. METHODS: A systematic review of the literature for studies examining HVPTC was performed. Four databases (PubMed, Scopus, OVID, Cochrane library) were queried from inception of databases through March 20th, 2020. RESULTS: Sixteen studies with 124 cases of HVPTC were included. The mean age for all patients was 52.3 years. HVPTC had a prevalence of 1.08% out of all PTC cases, with a mean tumor size of 3.1 cm. In 62% and 50% of cases, lymphovascular invasion and extrathyroidal extension were present, respectively. Follow-up data, with a mean of 49.9 months, revealed a 66% rate of lymph node metastasis and 23% rate of distant metastasis. Tumors with ≥30% hobnail morphology had a 2.6-fold increased odds of developing lymph node metastasis compared with <30% hobnail morphology, however did not differ in rates of distant metastasis. Patients ≥55 years old had a 4.5-fold increased odds of distant metastasis and a 4.7-fold increased odds of lymphovascular invasion over patients <55. CONCLUSIONS: High rates of locoregional and distant disease as well as high-risk pathological factors reveal the aggressive nature of HVPTC. Diagnostic criteria regarding percentage of hobnail morphology requires further refinement. Further studies are warranted in order to better understand how recognition of this high-risk variant impacts clinical treatment.

Randomized Controlled Trial of Technology-Assisted Case Management in Low Income Adults with Type 2 Diabetes.

OBJECTIVE: To assess the efficacy of technology-assisted case management (TACM) with medication titration by nurses using guideline-based algorithms, under physician supervision in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults (aged ≥18 years) from the southeastern United States with hemoglobin A1c [HbA1c] ≥8% were randomized to TACM or usual care. Evidence-based guidelines were used to develop medication titration algorithms in conjunction with clinic physicians. Participants were given a telehealth device that uploaded blood glucose and blood pressure readings daily to a central server. A nurse case manager was trained on the algorithms and authorized to titrate medications every 2 weeks based on the algorithm under the supervision of an internist and an endocrinologist. Participants were assessed at baseline, 3 months, and 6 months. The primary outcome was HbA1c at 6-months postrandomization in the intent-to-treat (ITT) population. RESULTS: One hundred thirteen participants were randomized to either TACM intervention or usual care. Based on ITT population after multiple imputation, the analysis of covariance with baseline HbA1c as covariate showed that HbA1c at 6 months for TACM was significantly lower compared to the usual care group (-0. 99, P = 0.024). Moreover, longitudinal mixed effects analysis suggested that the rate of decline in HbA1c over time for TACM was significantly faster compared to the usual care group (-0.16, P = 0.038). Results based on per-protocol population were similar. CONCLUSIONS: Technology-assisted case management by a nurse with medication titration under physician supervision is efficacious in improving glycemic control in low-income rural adults with poorly controlled type 2 diabetes.

Metabolic syndrome and periodontitis in Gullah African Americans with type 2 diabetes mellitus.

AIM: To assess associations of metabolic syndrome, and its individual components, with extent of severe periodontitis among patients with type 2 diabetes mellitus (T2DM). MATERIALS & METHODS: We performed a secondary data analysis (N = 283) using a cross-sectional study population of Gullah African Americans with T2DM. Extent of severe periodontitis was assessed as total diseased tooth-sites/person [evaluated as separate outcomes: 6+mm clinical attachment level (CAL), 5+mm periodontal probing depth (PPD)] using negative binomial regression techniques. Primary independent variables assessed in separate models included metabolic syndrome (yes/no), each metabolic syndrome component (low HDL, hypertension, high triglycerides, large waist circumference) and glycemic control (poor/good). RESULTS: Multivariable CAL-model results showed a significant association for metabolic syndrome status with extent of severe periodontitis (RR = 2.77, p = 0.03). The separate multivariable CAL-model including each metabolic syndrome component showed marginally increased rates among those with large waist circumference (RR = 2.33, p = 0.09) and those with HbA1c ≥ 7% (RR = 1.73, p = 0.06). Multivariable PPD-models showed marginally increased rates among those with metabolic syndrome (RR = 2.18, p = 0.06). CONCLUSION: Metabolic syndrome is associated with the extent of severe periodontitis in this Gullah population with T2DM.

Oral health and type 2 diabetes.

Type 2 diabetes mellitus has been described as a new epidemic. Approximately 285 million people worldwide suffer from diabetes, and this number is predicted to increase by approximately 50% by year 2030. This article will review oral health manifestations of diabetes and discuss associations between periodontal disease and diabetes. Although there is a strong body of evidence that supports the relationship between oral health and type 2 diabetes mellitus, oral health awareness is lacking among patients with diabetes and other health professionals. There is a need for the treating physician to be educated about the various oral manifestations of diabetes so that they can be diagnosed early and timely referrals to oral health specialists can be made. The established link between periodontitis and diabetes calls for an increased need to study ways to control both diseases, particularly among populations with health disparities and limited access to oral and health care.

Associations between health insurance and generalized periodontal disease in a study population of Gullah African Americans with type-2 diabetes.

OBJECTIVES: To explore the relationship between health insurance status (Medicare, Medicaid, private, and uninsured) and generalized periodontal disease (GPD) among a study population (N = 245) of adult Gullah African Americans with type-2 diabetes mellitus (T2DM) ages <65 years. METHODS: We used multivariable logistic regression to assess GPD [using three different and increasingly severe clinical assessments: 3, 4, and 5 mm clinical attachment level (CAL) at 30% of sites] according to health insurance status. RESULTS: Prevalence of GPD was 33.06% for 3, 18.78% for 4, and 9.80% for 5 mm CAL. Age ranged 26-64 years (mean = 52.11, SD = 8.53, median = 53). Private insurance was most prevalent (39.59%), followed by uninsured (30.61%), Medicaid (16.33%), and Medicare (13.47%). Results showed increased odds (versus private insurance) for GPD at 3 mm among Medicaid (OR = 1.82, P = 0.2404), Medicare (OR = 3.34, P = 0.0103), and uninsured (OR = 1.96, P = 0.0956) groups; GPD at 4 mm among Medicaid (OR = 1.97, P = 0.3303), Medicare (OR = 5.02, P = 0.0121), and uninsured (OR = 3.38, P = 0.0319) groups; and GPD at 5 mm among Medicaid (OR = 1.21, P = 0.8507), Medicare (OR = 12.62, P = 0.0038), and uninsured (OR = 4.00, P = 0.0763) groups. CONCLUSIONS: We observed substantial disparities for GPD severity among those without private health insurance even after adjusting for glycemic control, income, dental health behaviors, and other covariates. Improved insurance benefits as well as individualized oral health educational interventions may decrease GPD severity for this study population of younger (ages <65 years) Gullah African Americans with T2DM, particularly those with Medicare insurance.

Gene-centric meta-analysis of lipid traits in African, East Asian and Hispanic populations.

Meta-analyses of European populations has successfully identified genetic variants in over 100 loci associated with lipid levels, but our knowledge in other ethnicities remains limited. To address this, we performed dense genotyping of ∼2,000 candidate genes in 7,657 African Americans, 1,315 Hispanics and 841 East Asians, using the IBC array, a custom ∼50,000 SNP genotyping array. Meta-analyses confirmed 16 lipid loci previously established in European populations at genome-wide significance level, and found multiple independent association signals within these lipid loci. Initial discovery and in silico follow-up in 7,000 additional African American samples, confirmed two novel loci: rs5030359 within ICAM1 is associated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (p = 8.8×10(-7) and p = 1.5×10(-6) respectively) and a nonsense mutation rs3211938 within CD36 is associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 13.5×10(-12)). The rs3211938-G allele, which is nearly absent in European and Asian populations, has been previously found to be associated with CD36 deficiency and shows a signature of selection in Africans and African Americans. Finally, we have evaluated the effect of SNPs established in European populations on lipid levels in multi-ethnic populations and show that most known lipid association signals span across ethnicities. However, differences between populations, especially differences in allele frequency, can be leveraged to identify novel signals, as shown by the discovery of ICAM1 and CD36 in the current report.

Health insurance status is associated with periodontal disease progression among Gullah African-Americans with type 2 diabetes mellitus.

OBJECTIVES: Assess periodontal disease progression among GullahAfrican Americans with type 2 diabetes mellitus (T2DM) according to health insurance coverage. METHODS: From an ongoing clinical trial among T2DM Gullah, we extracted a cohort that was previously enrolled in a cross-sectional study (N=93). Comparing prior exam to trial initiation, total tooth sites/person with periodontal disease progression events [evaluated separately: 2+ mm of clinical attachment loss (CAL), 2+ mm increased periodontal probing depths (PPD), bleeding on probing (BOP) emergence] were evaluated according to health insurance coverage using regression techniques appropriate for data with different counts of potential events per subject (varying tooth sites available). We used negative binomial regression techniques to account for overdispersion and fit multivariable models that also included baseline glycemic control (poor: glycated hemoglobin > OR =7 percent, well: glycated hemoglobin <7 percent), history of established periodontitis, age, gender, body mass index, annual income, and oral hygiene behaviors. Final models included health insurance status, other significant predictors, and any observed confounders. RESULTS: Privately insured were most prevalent (41.94 percent), followed by uninsured (23.66 percent), Medicare (19.35 percent), and Medicaid (15.05 percent). Those with poor glycemic control (65.59 percent) were more prevalent than well-controlled (34.41 percent). CAL events ranged from 0 to 58.8 percent tooth sites/ person (11.83 +/- 12.44 percent), while PPD events ranged from 0 to 44.2 percent (8.66 +/- 10.97 percent) and BOP events ranged from 0 to 95.8 percent (23.65 +/- 17.21 percent). Rates of CAL events were increased among those who were uninsured [rate ratio (RR) = 1.75, P = 0.02], Medicare-insured (RR = 1.90, P = 0.03), and Medicaid-insured (RR = 1.89, P = 0.06). CONCLUSIONS: Increased access to health care, including dental services, may achieve reduction in chronic periodontal disease progression (as determined by CAL) for this study population. These results are very timely given the March 2010 passing of the US healthcare reform bills.

An evaluation of serum albumin, root caries, and other covariates in Gullah African Americans with type-2 diabetes.

OBJECTIVES: Associations between dental conditions and overall health have been previously reported. Investigators have also shown significant inverse relationships between serum albumin (a general health status marker) and root caries. This relationship was explored among a study population of Gullah African Americans (who have a considerably lower level of non-African genetic admixture when compared to other African American populations) with type-2 diabetes (T2DM) and self-reported history of normal kidney function (N=280). METHODS: Root caries indices were defined as total decayed and/or filled root surfaces. The coronal caries index [total decayed, missing, and/or filled coronal surfaces (DMFS)], level of glycemic control, total number of teeth, and other covariates were also evaluated. Logistic regression models were used to evaluate the associations between these factors and hypoalbuminemia (serum albumin concentrations <4 g/dl). RESULTS: Serum albumin concentrations ranged 2.4-4.5 g/dl (mean=3.8, SD=0.3), with 70.4% exhibiting hypoalbuminemia. Root caries totals ranged 0-38 (mean=1.3, SD=4.5) surfaces decayed/filled, while total teeth ranged 1-28 (mean=19.4, SD=6.2). DMFS totals ranged 2-116 (mean=55.2, SD=28.0). We failed to detect significant associations for root caries; however, the final multivariable logistic regression models showed significant associations between hypoalbuminemia and total teeth [odds ratio (OR)=0.93, P=0.01], poor glycemic control (OR=2.49, P<0.01), elevated C-reactive protein (OR=1.57, P<0.01), glomerular filtration rates ≥60 (OR=0.31, P=0.03), and age (OR=0.97, P=0.03). CONCLUSIONS: Previously reported inverse relationships between serum albumin and root caries were not evident in our study population. We propose that these null findings are because of the considerably lower level of root caries as well as other differing characteristics (including oral health status, the chronic presence of T2DM, and predominantly younger age) within our study population compared to these previously assessed groups.

Periodontal disease progression and glycaemic control among Gullah African Americans with type-2 diabetes.

AIM: To evaluate associations between glycaemic control and periodontitis progression among Gullah African Americans with type-2 diabetes mellitus (T2DM). MATERIALS AND METHODS: From an ongoing clinical trial among T2DM Gullah, we extracted a cohort previously in a cross-sectional study (N=88). Time from baseline (previous study) to follow-up (trial enrollment, before treatment interventions) ranged 1.93-4.08 years [mean=2.99, standard deviation (SD)=0.36]. We evaluated tooth site-level periodontitis progression [clinical attachment loss (CAL) worsening of > or =2 mm, periodontal probing depth (PPD) increases of > or =2 mm and bleeding on probing (BOP) from none to present] by glycaemic control status (well-controlled=HbA(1c)<7%, poorly-controlled=HbA(1c)> or =7%) using multivariable generalized estimating equations logistic regression, nesting tooth sites/person. RESULTS: Poorly-controlled T2DM (68.18%) was more prevalent than well-controlled T2DM (31.82%). Proportions of tooth sites/person with CAL progression between baseline and follow-up ranged 0.00-0.59 (mean=0.12, SD=0.12), while PPD and BOP progression ranged 0.00-0.44 (mean=0.09, SD=0.11) and 0.00-0.96 (mean=0.24, SD=0.18), respectively. Site-level PPD at baseline was a significant effect modifier of associations between poorly-controlled T2DM and site-level CAL and PPD progression [adjusted odds ratios (OR) according to poorly-controlled T2DM among PPD at baseline=3, 5 and 7 mm, respectively: CAL progression=1.93, 2.64, and 3.62, PPD progression=1.98, 2.76, and 3.84; p<0.05 for all]. Odds of site-level BOP progression were increased (OR=1.24) for poorly-controlled T2DM, yet the results were not significant (p=0.32). CONCLUSIONS: These findings from a distinct, homogenous population further support the clinical relevance of identifying patients with poor glycaemic control and periodontitis, particularly among those with disparities for both diseases.

The genetic architecture of lipoprotein subclasses in Gullah-speaking African American families enriched for type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR).

We sought to partition the genetic and environmental influences on lipoprotein subclasses and identify genomic regions that may harbor genetic variants that influence serum lipoprotein levels in a sample of Gullah-speaking African-Americans. We genotyped 5,974 SNPs in 979 subjects from 418 pedigrees and used the variance component approach to compute heritability estimates, genetic and environmental correlations, and linkage analyses for selected lipoprotein subclasses. The highest heritability estimate was observed for large VLDL particle concentration (0.56 +/- 0.14). Mean LDL particle size and small LDL particle concentration (-0.94) had the strongest genetic correlation estimate. The highest logarithm of odds (LOD) score detected (3.0) was on chromosome 6p24 for small LDL particle concentration. The strongest signal, obtained with the reduced sample of diabetic individuals only, was observed on chromosome 20p13 for small LDL particle concentration. The highest bivariate linkage signal (LOD 2.4) was observed on chromosome 6p24 for mean LDL particle size and small LDL particle concentration. Our results suggest a significant genetic contribution to multiple lipoprotein subclasses studied in this sample and that novel loci on chromosomes 6, 10, 16, and 20 may harbor genes contributing to small, atherogenic LDL particle concentration and large, triglyceride-rich VLDL particle concentration.

Periodontal disease status in gullah african americans with type 2 diabetes living in South Carolina.

BACKGROUND: African Americans have a disproportionate burden of diabetes. Gullah African Americans are the most genetically homogeneous population of African descent in the United States, with an estimated European admixture of only 3.5%. This study assessed the previously unknown prevalence of periodontal disease among a sample of Gullah African Americans with diabetes and investigated the association between diabetes control and the presence of periodontal disease. METHODS: Two hundred thirty-five Gullah African Americans with type 2 diabetes were included. Diabetes control was assessed by percentage of glycosylated hemoglobin (HbA1c) and divided into three categories: well controlled, <7%; moderately controlled, 7% to 8.5%; and poorly controlled, >8.5%. Participants were categorized as healthy (no clinical attachment loss [AL] or bleeding on probing) or as having early periodontitis (clinical AL > or =1 mm in at least two teeth), moderate periodontitis (three sites with clinical AL > or =4 mm and at least two sites with probing depth [PD] > or =3 mm), or severe periodontitis (clinical AL > or =6 mm in at least two teeth and PD > or =5 mm in at least one site). Observed prevalences of periodontitis were compared to rates reported for the National Health and Nutrition Examination Survey (NHANES) studies. RESULTS: All subjects had evidence of periodontal disease: 70.6% had moderate periodontitis and 28.5% had severe disease. Diabetes control was not associated with periodontal disease. The periodontal disease proportions were significantly higher than the reported national prevalence of 10.6% among African Americans without diabetes. CONCLUSION: Our sample of Gullah African Americans with type 2 diabetes exhibited a higher prevalence of periodontal disease compared to African Americans, with and without diabetes, as reported in NHANES III and NHANES 1999-2000.

Genome-wide linkage scan in Gullah-speaking African American families with type 2 diabetes: the Sea Islands Genetic African American Registry (Project SuGAR).

OBJECTIVE: The Gullah-speaking African American population from the Sea Islands of South Carolina is characterized by a low degree of European admixture and high rates of type 2 diabetes and diabetic complications. Affected relative pairs with type 2 diabetes were recruited through the Sea Islands Genetic African American Registry (Project SuGAR). RESEARCH DESIGN AND METHODS: We conducted a genome-wide linkage scan, genotyping 5,974 single nucleotide polymorphisms in 471 affected subjects and 50 unaffected relatives from 197 pedigrees. Data were analyzed using a multipoint engine for rapid likelihood inference and ordered subsets analyses (OSAs) for age at type 2 diabetes diagnosis, waist circumference, waist-to-hip ratio, and BMI. We searched for heterogeneity and interactions using a conditional logistic regression likelihood approach. RESULTS: Linkage peaks on chromosome 14 at 123-124 cM were detected for type 2 diabetes (logarithm of odds [LOD] 2.10) and for the subset with later age at type 2 diabetes diagnosis (maximum LOD 4.05). Two linkage peaks on chromosome 7 were detected at 44-45 cM for type 2 diabetes (LOD 1.18) and at 78 cM for type 2 diabetes (LOD 1.64) and the subset with earlier age at type 2 diabetes diagnosis (maximum LOD 3.93). The chromosome 14 locus and a peak on 7p at 29.5 cM were identified as important in the multilocus model. Other regions that provided modest evidence for linkage included chromosome 1 at 167.5 cM (LOD 1.51) and chromosome 3 at 121.0 cM (LOD 1.61). CONCLUSIONS: This study revealed a novel type 2 diabetes locus in an African American population on 14q that appears to reduce age of disease onset and confirmed two loci on chromosome 7.

Anaplastic thyroid carcinoma: an overview.

Thyroid cancer is an uncommon malignancy that accounts for roughly 1% of all new cancers. Although anaplastic lesions constitute fewer than 5% of thyroid cancers, they represent over half of thyroid cancer-related deaths. The relative rarity of anaplastic thyroid cancer, its aggressive nature, and its rapidly fatal course have contributed to the difficulty in developing effective treatment for this disease. Radiation, chemotherapy, and surgery are rarely curative, but combinations of these modalities appear to offer greater benefit than any single treatment. New treatment modalities are desperately required, and promising molecular-based therapies are being investigated.

Overview of the management of differentiated thyroid cancer.

Thyroid cancer is an uncommon tumor accounting for roughly 1% of all new malignancies. Differentiated (ie, papillary or follicular) thyroid carcinoma is usually asymptomatic, and frequently appears as a solitary thyroid nodule but few show cervical lymphadenopathy or metastasis to lung, bone, or liver. Fine needle aspiration (FNA) is recommended in the initial diagnostic test. Depending on the size of the lesion and other associated risk factors, most patients are treated with total or near total thyroidectomy. Postoperative radioiodine ablation is performed when tumor has a potential for recurrence. Recurrence rates and cancer-specific mortality is decreased by suppressing thyroid stimulating hormone (TSH). Long-term surveillance and follow-up with physical examination every 3 to 6 months for 2 years and then annually if patient remains cancer free. Whole body iodine scans are done every 12 months for follow-up until one negative scan (either withdrawal of thyroid hormone or rhodium complex -TSH). Thyroglobulin measurements (with antithyroglobulin antibodies) and ultrasound neck are suggested at 6 and 12 months and then annually if disease free.