Phylogenetic analysis of human G9P[8] rotavirus strains circulating in Jiangsu,China between 2010 and 2016

Rotavirus A (RVA) is the leading cause of acute viral gastroenteritis in children under 5 years of age worldwide. G9P[8] is a common RVA genotype that has been persistently prevalent in Jiangsu, China. To determine the genetic diversity of G9P[8] RVAs, 7 representative G9P[8] strains collected from Suzhou Children’s Hospital between 2010 and 2016 (named JS2010‐JS2016) were analyzed through whole‐genome sequencing. All evaluated strains showed the Wa‐like constellation G9‐P[8]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1. Furthermore, phylogenetic analysis revealed that the VP7 genes of all strains clustered into lineage G9‐III and G9‐VI. With the exception of strain JS2012 (P[8]‐4), the VP4 sequences of all strains belonged to the P[8]‐3 lineage. Sequencing further revealed that amino acid substitutions were present in the antigenic regions of the VP7 and VP4 genes of all strains. Moreover, there were multiple substitutions in antigenic sites I and II of the nonstructural protein 4 (NSP4) genes, whereas the other NSP genes were relatively conserved. In conclusion, our phylogenetic analysis of these 7 G9P[8] strains suggests that RVA varied across regions and time. Therefore, our findings suggest that continued surveillance is necessary to explore the molecular evolutionary characteristics of RVA for better prevention and treatment of acute viral gastroenteritis.     

Genes and (auto)immunity in primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic autoimmune cholestatic liver disease most commonly encountered in postmenopausal women; it is characterized by high-titer serum autoantibodies to mitochondrial antigens, elevated serum IgM, progressive destruction of intrahepatic bile ducts, and ultimately liver cirrhosis and failure. The cytopathic mechanisms leading to the selective destruction of intrahepatic cholangiocytes are still largely unknown. The current theory on the pathogenesis of PBC indicated that environmental factors might trigger autoimmunity in genetically susceptible individuals. In fact, genetic predisposition is critical to disease onset and progression, yet peculiar among autoimmune diseases, as indicated by the lack of a strong association with major histocompatibility complex haplotypes. Further, the recently reported concordance rate among monozygotic twins strengthens the importance of genetic factors, while also indicating that additional factors, possibly infectious agents or xenobiotics, intervene to trigger the disease. In this review, the available data regarding the genetic factors associated with PBC susceptibility and progression, as well as the available evidence regarding the immunomediated pathogenesis of PBC, will be critically illustrated and discussed.     

Follicular density in ovarian biopsy of infertile women: a novel method to assess ovarian reserve

The ageing ovary appears to be characterized by depletion of primordial follicles. The relationship between infertility and the number of follicles in the ovarian cortex is not known. Moreover, there are no accurate markers or clinical methods to predict the decline in ovarian reserve. This study investigates the correlation between early follicular follicle stimulating hormone, ovarian size and follicular density in 60 infertile women aged 19-45 years (mean = 34.4 +/- 5.5). An ovarian biopsy was taken from each patient while performing diagnostic laparoscopy (n = 28) or laparotomy for tubal surgery or myomectomy (n = 32). The median number of follicles was similar in tubal and unexplained infertility patients (9.5 versus 5.5). Increasing age showed a significant negative correlation with follicular density and ovarian volume (r = -0.46, P = 0.0003;. r = -0.43, P = 0.0016, respectively). In women > or = 35 years of age the ovarian volume showed a strong correlation with follicular density (r = 0.71, P < 0.0001). Our results indicate that infertile women in their late thirties and over have a decreased ovarian reserve which could possibly be predicted by ovarian volume measurement. Ovarian biopsy may have a place as part of infertility evaluation in older women.      

Ancestry informative marker sets for determining continental origin and admixture proportions in common populations in America

To provide a resource for assessing continental ancestry in a wide variety of genetic studies, we identified, validated, and characterized a set of 128 ancestry informative markers (AIMs). The markers were chosen for informativeness, genome-wide distribution, and genotype reproducibility on two platforms (TaqMan assays and Illumina arrays). We analyzed genotyping data from 825 subjects with diverse ancestry, including European, East Asian, Amerindian, African, South Asian, Mexican, and Puerto Rican. A comprehensive set of 128 AIMs and subsets as small as 24 AIMs are shown to be useful tools for ascertaining the origin of subjects from particular continents, and to correct for population stratification in admixed population sample sets. Our findings provide general guidelines for the application of specific AIM subsets as a resource for wide application. We conclude that investigators can use TaqMan assays for the selected AIMs as a simple and cost efficient tool to control for differences in continental ancestry when conducting association studies in ethnically diverse populations.     

Association of PDCD1 genetic variation with risk and clinical manifestations of systemic lupus erythematosus in a multiethnic cohort

We evaluated the roles of five single-nucleotide polymorphisms (SNPs) within PDCD1, and haplotypes defined by these SNPs, for the development of systemic lupus erythematosus (SLE) and specific sub-phenotypes (nephritis, antiphospholipid antibody positive, arthritis and double-stranded DNA positive) within a multiethnic US cohort of 1036 patients. Family based analyses were performed using 844 simplex families from four ethnic groups (Caucasian, Asian, Hispanic and African American). Subjects were genotyped for five 'tag' SNPs (selected from 15) to provide complete genetic information in all main ethnic groups. We employed transmission disequilibrium testing to assess risk for SLE by allele or haplotype, and multiple logistic regression analysis of SLE cases to examine associations with specific sub-phenotypes. In family based analyses, a haplotype containing the PD1.3A allele was significantly associated with SLE susceptibility among Caucasian families (P=0.01). Among Hispanic families, two novel SNPs were associated with SLE risk (P=0.005 and 0.01). In multivariate logistic regression analyses, five haplotypes were associated with specific sub-phenotypes among the different ethnic groups. These results suggest that PDCD1 genetic variation influences the risk and expression of SLE and that these associations vary according to ethnic background.     

Nephrolithiasis and bone involvement in primary hyperparathyroidism

PURPOSE: The purpose of this study was to compare patients with primary hyperparathyroidism with and without nephrolithiasis with regard to (1) biochemical profile, and (2) presence and extent of bone involvement. PATIENTS AND METHODS: Of 70 unselected patients enrolled in a longitudinal study on the natural history of primary hyperparathyroidism, 62 who underwent complete bone densitometry evaluation were considered. The patients had mild hypercalcemia (2.77 +/- 0.02 mmol/L), as well as elevated parathyroid hormone levels by mid-molecule, N-terminal, and immunoradiometric assays. Bone densitometry was assessed by dual-photon absorptiometry of the lumbar spine and femoral neck, and single-photon absorptiometry of the forearm. RESULTS: Eleven of the 62 patients (18%) had nephrolithiasis. There was no difference in serum parathyroid hormone levels, calcium, phosphorus, serum 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D3 between those with and without kidney stones. Total daily urinary calcium excretion was higher among those who formed stones (8.2 +/- 1.0 mmol versus 6.1 +/- 0.4 mmol, p less than 0.05), but not when expressed per mmol of creatinine (0.72 +/- 0.07 versus 0.69 +/- 0.04). Urinary hydroxyproline was also higher in patients who formed stones (58 +/- 11 mg/24 hours versus 37 +/- 2 mg/24 hours; p less than 0.05). Hypercalciuria occurred in 39% of the entire cohort (n = 24), and in 33% (n = 17) of those without stones. Only 29% (n = 7) of those with hypercalciuria had nephrolithiasis. Calcium excretion correlated positively with serum 1,25-dihydroxyvitamin D3 (r = +0.32, p less than 0.05), and negatively with forearm bone mineral density (all patients: r = -0.34, p less than 0.05; hypercalciuric patients: r = -0.53, p less than 0.05). Circulating 1,25-dihydroxyvitamin D3 levels were elevated in a similar proportion of (1) all patients (31%, n = 19); (2) those with nephrolithiasis (27%); and (3) those without stones (31%). Bone mineral density was less than 80% of normal in 61% of patients, but forearm, femoral neck, and lumbar spine density were indistinguishable among those with and without stones. CONCLUSIONS: Cortical bone demineralization occurs to the same extent and frequency in patients with and without nephrolithiasis, and these two subgroups share similar biochemical and bone densitometric profiles. The pathophysiologic events leading to renal and skeletal involvement in primary hyperparathyroidism may be less selective than previously believed, as evidenced by: (1) increased urinary hydroxyproline in patients with nephrolithiasis, and (2) documentation that urinary calcium excretion reflects not only vitamin D status, but bone resorption was well.     

Radiolabeled Monoclonal Antibody Indium 111-Labeled CYT-356 Localizes Extraprostatic Recurrent Carcinoma After Prostatectomy

Objectives. The sites of recurrent carcinoma of the prostate were localized with radiolabeled monoclonal antibody, and these sites were correlated with the response of patients treated with pelvic radiation after prostatectomy.Methods. Radionuclide scans were performed with indium 111-labeled CYT-356, a monoclonal antibody that binds to prostate epithelial cells, in 48 men diagnosed with recurrent carcinoma detected by prostate-specific antigen (PSA) screening after radical retropubic prostatectomy.Results. In 48 patients with recurrent carcinoma detected by PSA screening following radical retropubic prostatectomy, 73% had monoclonal antibody activity beyond the prostatic fossa, and only 3 patients (6%) had activity in the prostatic fossa alone; 65% had monoclonal antibody activity in pelvic lymph nodes despite the fact that lymph node dissections were pathologically negative at the time of prostatectomy in 90% of the patients; and 23% of patients had monoclonal antibody activity in abdominal and extrapelvic retroperitoneal nodes. Of 48 patients, 13 underwent external beam radiation therapy after monoclonal antibody scans. Six patients had scans showing activity beyond the field of radiation, and radiation therapy failed in 4 of these patients. Seven patients had scans with no activity beyond the field of radiation therapy, and radiation therapy failed in only 2 of these patients.Conclusions. The scans frequently show monoclonal antibody uptake in pelvic, abdominal, and extrapelvic retroperitoneal sites beyond the region of limited obturator node dissections and may account for the understaging and subsequent failure of radical prostatectomy in some patients. The monoclonal antibody scan seems to be a good predictor of which patients will respond to radiation therapy after radical prostatectomy, but because these patients often have nodal activity beyond the radiated field, this initial response may not be curative.     

Review and Management of the Dental Patient With Long QT Syndrome (LQTS)

Long QT syndrome (LQTS) is a unique cardiovascular condition, with both congenital and acquired forms that afflict patients. These patients show a lengthening of the repolarization phase of the cardiac cycle, which can be best visualized on an electrocardiogram (ECG). The ECG changes can include QT interval (the time between the start of the Q wave and the end of the T wave, as seen on an ECG) and T wave abnormalities, as well as progression to torsades de pointes and ventricular fibrillation. The ECG changes are most commonly elicited by physical activity, emotional stress, and certain medications. This condition represents a challenge for the oral and maxillofacial surgeon. Patients with LQTS must receive proper medical management and a controlled and anxiety-free surgical environment. The purpose of this article was to present a review of LQTS and provide recommendations for effective surgical management. Additionally, a case report of a patient with LQTS, treated by one of the authors, has been included.