Association of Multiple Aggregated Yellow-White Globules With Nonpigmented Basal Cell Carcinoma.

Importance: Basal cell carcinoma (BCC) is the most common skin cancer. Dermoscopic imaging has improved diagnostic accuracy; however, diagnosis of nonpigmented BCC remains limited to arborizing vessels, ulceration, and shiny white structures. Objective: To assess multiple aggregated yellow-white (MAY) globules as a diagnostic feature for BCC. Design, Setting, and Participants: In this retrospective, single-center, case-control study, nonpigmented skin tumors, determined clinically, were identified from a database of lesions consecutively biopsied during a 7-year period (January 1, 2009, to December 31, 2015). A subset of tumors was prospectively diagnosed, and reflectance confocal microscopy, optical coherence tomography, and histopathologic correlation were performed. Data analysis was conducted from July 1 to September 31, 2019. Exposures: Investigators evaluated for the presence or absence of known dermoscopic criteria. MAY globules were defined as aggregated, white-yellow structures visualized in polarized and nonpolarized light. Main Outcomes and Measures: The primary outcome was the diagnostic accuracy of MAY globules for the diagnosis of BCC. Secondary objectives included the association with BCC location and subtype. Interrater agreement was estimated. Results: A total of 656 nonpigmented lesions from 643 patients (mean [SD] age, 63.1 [14.9] years; 381 [58.1%] male) were included. In all, 194 lesions (29.6%) were located on the head and neck. A total of 291 (44.4%) were BCCs. MAY globules were seen in 61 of 291 BCC cases (21.0%) and in 3 of 365 other diagnoses (0.8%) (P < .001). The odds ratio for diagnosis of BCC was 32.0 (96% CI, 9.9-103.2). The presence of MAY globules was associated with a diagnosis of histologic high-risk BCC (odds ratio, 6.5; 95% CI, 3.1-14.3). The structure was never seen in cases of superficial BCCs. Conclusions and Relevance: The findings suggest that MAY globules may have utility as a new BCC dermoscopic criterion with a high specificity. MAY globules were negatively associated with superficial BCC and positively associated with deeper-seated, histologic, higher-grade tumor subtypes.

Overview of a chemoresponse assay in ovarian cancer.

The objective of this review is to summarize recent scientific and medical literature regarding chemoresponse assays or chemotherapy sensitivity and resistance assays (CSRAs), specifically as applied to epithelial ovarian cancer. A total of sixty-seven articles, identified through PubMed using the key words "in vitro chemoresponse assay," "chemo sensitivity resistance assay," "ATP," "HDRA," "EDR," "MiCK," and "ChemoFx," were reviewed. Recent publications on marker validation, including relevant clinical trial designs, were also included. Recent CSRA research and clinical studies are outlined in this review. Published findings demonstrate benefits regarding patient outcome with respect to recent CSRAs. Specifically, analytical and clinical validations, as well as clinical utility and economic benefit, of the most common clinically used CSRA in the United States support its use to aid in making effective, individualized clinical treatment selections for patients with ovarian cancer.

A randomized non-inferiority study comparing the addition of exenatide twice daily to sitagliptin or switching from sitagliptin to exenatide twice daily in patients with type 2 diabetes experiencing inadequate glycaemic control on metformin and sitagliptin.

AIMS: To test the hypothesis that glycaemic control achieved when switching sitagliptin to exenatide twice daily plus metformin is non-inferior to adding exenatide twice daily to sitagliptin and metformin. METHODS: Patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin were randomly assigned to 20 weeks of treatment with twice-daily exenatide plus placebo and metformin (SWITCH, n = 127) or twice-daily exenatide plus sitagliptin and metformin (ADD, n = 128). RESULTS: Non-inferiority (0.4% margin) of SWITCH to ADD treatment, measured by change in HbA(1c) from baseline to week 20, was not shown {between-treatment difference in least-squares mean [95% CI 3 mmol/mol (0.30%)] [0.8-5.8 (0.07-0.53)]}. A greater reduction (P = 0.012) in HbA(1c) [least-squares mean (se)] was experienced by patients in the ADD group {-7 mmol/mol [-0.68%] [0.9 (0.08)]}, compared with those in the SWITCH group {-4 mmol/mol [-0.38%] [1.0 (0.09)]} and a greater proportion (P = 0.027) of patients in the ADD group (41.7%) reached < 7.0% (< 53 mmol/mol) HbA(1c) target, compared with those in the SWITCH group (26.6%) by week 20. Patients in the ADD group experienced greater fasting serum glucose (P = 0.038) and daily mean postprandial self-monitored blood glucose (P = 0.048) reductions, compared with patients in the SWITCH group, by week 20. Patients in both groups experienced a lower incidence of nausea and vomiting compared with previous exenatide studies. CONCLUSIONS: Non-inferiority of SWITCH to ADD treatment was not supported by the results of this study. In patients with Type 2 diabetes inadequately controlled with sitagliptin plus metformin, adding exenatide provided better glycaemic control than switching to exenatide. These results are consistent with the clinical approach that adding is better than switching to another oral anti-hyperglycaemic medication.

Patients' education, and its impact on care outcomes, resource consumption and working conditions: data from the International Diabetes Management Practices Study (IDMPS).

AIM: To evaluate the impact of diabetes education provided to patients with type 2 diabetes mellitus (T2DM) in non-controlled studies ("real-world conditions") on quality of care, resource consumption and conditions of employment. METHODS: This cross-sectional study and longitudinal follow-up describe the data (demographic and socioeconomic profiles, clinical characteristics, treatment of hyperglycaemia and associated cardiovascular risk factors, resource consumption) collected during the second phase (2006) of the International Diabetes Management Practices Study (IDMPS). Patients received diabetes education directly from the practice nurse, dietitian or educator, or were referred to ad hoc group-education programmes; all programmes emphasized healthy lifestyle changes, self-care and active participation in disease control and treatment. Educated vs non-educated T2DM patients (n=5692 in each group), paired by age, gender and diabetes duration, were randomly recruited for the IDMPS by participating primary-care physicians from 27 countries in Eastern Europe, Asia, Latin America and Africa. Outcome measures included clinical (body weight, height, waist circumference, blood pressure, foot evaluation), metabolic (HbA(1c) levels, blood lipid profile) and biochemical control measures. Treatment goals were defined according to American Diabetes Association guidelines. RESULTS: T2DM patients' education significantly improved the percentage of patients achieving target values set by international guidelines. Educated patients increased their insulin use and self-care performance, had a lower rate of chronic complications and a modest increase in cost of care, and probably higher salaries and slightly better productivity. CONCLUSION: Diabetes education is an efficient tool for improving care outcomes without having a major impact on healthcare costs.

Autoantibodies to a miRNA-binding protein Argonaute2 (Su antigen) in patients with hepatitis C virus infection.

OBJECTIVES: Chronic liver diseases caused by hepatitis B (HBV) or C virus (HCV) are common worldwide. Despite reports on autoimmunity in viral hepatitis, studies on autoantibodies associated with systemic rheumatic diseases are inconsistent. Testing of a small number of selected autoantibody specificities using ELISA appears to be one reason for inconsistency. Sera from patients with viral hepatitis were tested by immunoprecipitation that will allow unbiased screening of autoantibodies found in systemic rheumatic diseases. METHODS: Ninety Mexican patients (37 male, 53 female, 26 HBV, 6 HBV+HCV, 58 HCV) with chronic viral hepatitis, confirmed by nested or RT-nested-PCR, HBsAg and anti-HCV antibodies, were studied. Autoantibodies were tested by immunofluorescence, immunoprecipitation and ELISA. Specificities were verified using reference sera. RESULTS: Antinuclear antibodies were found in 38% HBV, 17% HBV+HCV, and 28% in HCV. Autoantibodies to Argonaute (Ago2, Su antigen), a microRNA binding protein that plays a key role in RNA-induced silencing complex (RISC), was found in 5% (4/64) of HCV or HBV+HCV coinfected patients but not in HBV (0/26). Anti-Ago2/Su was found in 1/2 of I-IFN-treated case vs. 3/62 in cases without I-IFN. HCV did not have other lupus autoantibodies whereas 19% (5/26) of HBV had anti-U1RNP+Ku, Ro+La, RNA polymerase II, or possible U5snRNPs. CONCLUSIONS: Lupus autoantibodies were uncommon in HCV except anti-Ago2/Su. HCV and I-IFN have many ways to affect TLR signaling, miRNA and miRNA binding protein Ago2/Su. To understand the mechanism of specific targeting of Ago2 in HCV may provide a clue to understand the mechanism of specific autoantibody production.

Effect of a combination DNA vaccine for the prevention and therapy of Trypanosoma cruzi infection in mice: role of CD4+ and CD8+ T cells.

Chagas disease is a major public health problem, with about 10 million infected people, and DNA vaccines are a promising alternative for the control of Trypanosoma cruzi, the causing agent of the disease. We tested here a new DNA vaccine encoding a combination of two leading parasite antigens, TSA-1 and Tc24, for the prevention and therapy of T. cruzi infection. Immunized Balb/c mice challenged by T. cruzi presented a significantly lower parasitemia and inflammatory cell density in the heart compared to control mice. Similarly, the therapeutic administration of the DNA vaccine was able to significantly reduce the parasitemia and inflammatory reaction in acutely infected Balb/c and C57BL/6 mice, and reduced cardiac tissue inflammation in chronically infected ICR mice. Therapeutic vaccination induced a marked increase in parasite-specific IFNγ producing CD4(+) and CD8(+) T cells in the spleen as well as an increase in CD4(+) and CD8(+) T cells in the infected cardiac tissue. In addition, some effect of the DNA vaccine could still be observed in CD4-knockout C57BL/6 mice, which presented a lower parasitemia and inflammatory cell density, but not in CD8-deficient mice, in which the vaccine had no effect. These results indicate that the activation of CD8(+) T cells plays a major role in the control of the infection by the therapeutic DNA vaccine, and to a somewhat lesser extent CD4(+) T cells. This observation opens interesting perspectives for the potentiation of this DNA vaccine candidate by including additional CD8(+) T cell antigens/epitopes in future vaccine formulations.

Comparison of insulin lispro protamine suspension and insulin detemir in basal-bolus therapy in patients with Type 1 diabetes.

AIMS: The efficacy of two basal insulins, insulin lispro protamine suspension (ILPS) and insulin detemir, was compared in basal-bolus regimens in Type 1 diabetes. METHODS: In this 32-week, multinational, parallel-group, randomized, controlled trial, adult patients with Type 1 diabetes received ILPS or insulin detemir, injected twice daily (before breakfast and bedtime) and prandial insulin lispro three times daily. The primary outcome was change in glycated haemoglobin (HbA(1c)) from baseline to endpoint. RESULTS: Least squares mean (+/-se) changes in HbA(1c) were similar between groups, meeting non-inferiority (margin, 0.4%): -0.69 +/- 0.07% for ILPS and -0.59 +/- 0.07% for insulin detemir [between-treatment difference -0.10%; 95% confidence interval (CI) -0.29, 0.10]. Standard deviation of fasting blood glucose was similar (non-inferiority margin 0.8 mmol/l): 2.74 +/- 0.14 mmol/l for ILPS and 2.38 +/- 0.14 mmol/l for insulin detemir (CI -0.03, 0.75). Patients on ILPS gained more weight (1.59 +/- 0.23 kg vs. 0.62 +/- 0.24 kg; CI 0.34, 1.60; margin 1.5 kg). Weight-adjusted daily total and prandial insulin doses were lower for ILPS (prandial insulin, 0.38 +/- 0.01 U/kg/day for ILPS, 0.44 +/- 0.01 U/kg/day for insulin detemir; P = 0.004); daily basal insulin dose was similar. All hypoglycaemia incidence and rate and nocturnal hypoglycaemia incidence were similar between groups; nocturnal hypoglycaemia rate was lower for insulin detemir (mean +/- sd 0.79 +/- 1.23 for ILPS, 0.49 +/- 0.85 for insulin detemir; P = 0.001). Severe hypoglycaemia rate was 0.03 +/- 0.11 for ILPS and 0.02 +/- 0.10 for insulin detemir (P = 0.37). CONCLUSIONS: ILPS-treated patients with Type 1 diabetes achieved similar glycaemic control as insulin detemir-treated patients after 32 weeks. Glucose variability was similar. While weight gain and nocturnal hypoglycaemia rate were statistically higher with ILPS, the clinical relevance is unclear.

Detection of a SERK-like gene in coconut and analysis of its expression during the formation of embryogenic callus and somatic embryos.

Somatic embryogenesis involves different molecular events including differential gene expression and various signal transduction pathways. One of the genes identified in early somatic embryogenesis is S OMATIC E MBRYOGENESIS R ECEPTOR-like K INASE (SERK). Cocos nucifera (L.) is one of the most recalcitrant species for in vitro regeneration, achieved so far only through somatic embryogenesis, although just a few embryos could be obtained from a single explant. In order to increase efficiency of this process we need to understand it better. Therefore, the purpose of the present work was to determine if an ortholog of the SERK gene is present in the coconut genome, isolate it and analyze its expression during somatic embryogenesis. The results showed the occurrence of a SERK ortholog referred to as CnSERK. Predicted sequence analysis showed that CnSERK encodes a SERK protein with the domains reported in the SERK proteins in other species. These domains consist of a signal peptide, a leucine zipper domain, five LRR, the Serine-Proline-Proline domain, which is a distinctive domain of the SERK proteins, a single transmembrane domain, the kinase domain with 11 subdomains and the C terminal region. Analysis of its expression showed that it could be detected in embryogenic tissues before embryo development could be observed. In contrast it was not detected or at lower levels in non-embryogenic tissues, thus suggesting that CnSERK expression is associated with induction of somatic embryogenesis and that it could be a potential marker of cells competent to form somatic embryos in coconut tissues cultured in vitro.

Growth in children with moderate renal insufficiency: measurement, evaluation, and treatment.

Essential in the treatment of children with chronic renal insufficiency (CRI) is the elimination of growth deficits. With the prospect of recombinant human growth hormone (rhGH) and other adjunct treatment, the appropriate measurement and assessment of growth retardation and growth recovery will document continued progress toward eliminating this disabling condition. Phases and determinants of growth at different ages are best described by growth velocity patterns. Nutritional, hormonal, and metabolic determinants interact throughout each phase of growth. Potential for growth loss and recovery is greatest during infancy and early childhood, as shown by the growth velocity index (GVI) of change in height standard deviation score (SDS) (deltaHt - SDS) divided by the growth velocity - SDS (GV - SDS) (GVI = deltaHT - SDS/GV - SDS). An appropriate target height based on potential from mid-parental heights should be set before intervention to establish goals for duration of treatment. Ultimate adult height is the only true measurement of outcome, although predictive formulas based on parental heights and bone age versus chronologic age (BA/CA) are mathematic tools to gauge the efficacy of ongoing regimes. True catch-up growth is defined as the full recovery of lost percentiles and cannot be assumed with an increase in growth velocity or incremental gain in Ht-SDS.

A prospective, double-blind study of growth failure in children with chronic renal insufficiency and the effectiveness of treatment with calcitriol versus dihydrotachysterol. The Growth Failure in Children with Renal Diseases Investigators.

Because controlled trials in adults have shown accelerated deterioration of renal function in a small number of patients receiving calcitriol for renal osteodystrophy, we initiated a prospective, randomized, double-blind study of the use of calcitriol versus dihydrotachysterol in children with chronic renal insufficiency. We studied children aged 1 1/2 through 10 years, with a calculated glomerular filtration rate between 20 and 75 ml/min per 1.73 m2, and with elevated serum parathyroid hormone concentrations. Ninety-four patients completed a mean of 8.0 months of control observations and were randomly assigned to a treatment period; 82 completed the treatment period of at least 6 months while receiving a calcitriol dosage (mean +/- SD) of 17.1 +/- 5.9 ng/kg per day or a dihydrotachysterol dosage of 13.8 +/- 3.3 micrograms/kg per day. With treatment the height z scores for both calcitriol- and dihydrotachysterol-treated groups showed no differences between the two groups. In relation to cumulative dose, there was a significant decrease in glomerular filtration rate for both calcitriol and dihydrotachysterol; for calcitriol the rate of decline was significantly steeper (p = 0.0026). The treatment groups did not differ significantly with respect to the incidence of hypercalcemia (serum calcium concentration > 2.7 mmol/L (> 11 mg/dl)). We conclude that careful follow-up of renal function is mandatory during the use of either calcitriol or dihydrotachysterol because both agents were associated with significant declines in renal function. There was no significant difference between calcitriol and dihydrotachysterol in promoting linear growth or causing hypercalcemia in children with chronic renal insufficiency. Dihydrotachysterol, the less costly agent, can be used with equal efficacy.

Management of neonatal Graves disease with iopanoic acid.

An infant with thyrotoxicosis whose mother had Graves disease was treated with sodium iopanoate. Euthyroid status was achieved rapidly and maintained with minimal effort in comparison with the conventional multidrug regimen. There were no toxic effects, and hypothyroidism did not occur.

Mexican-American migrant students' academic success: sociological and psychological acculturation.

This study attempted to describe and compare academically successful and academically unsuccessful high-risk Mexican-American migrant high school students. The two groups were compared on sociological and psychological indicators of acculturation, urbanization, and socioeconomic status (SES). It was hypothesized that the successful group would have higher SES, be more acculturated, urbanized, and psychologically adjusted to modern value systems, and have higher occupational aspirations and expectations than the unsuccessful group. In addition, their world views were compared by exploring early recollection data. The results showed that the unsuccessful group came from families that were larger, poorer, more rural, and more "foreign" (i.e., more parents and children born in Mexico) than the successful students' families. Regarding the psychological indicators of acculturation, the successful group was found to score higher on modernism, to be more stably acculturated, to have a clearer sense of themselves, to have higher occupational aspirations and expectations, and tended to desire jobs with greater responsibility and stability than did the unsuccessful group.

Descriptions of the participating centers and patient population in the Growth Failure in Children with Renal Diseases Study.

The Growth Failure in Children With Renal Diseases Study, a double-blind, multicenter clinical trial with 108 children entered into the control period over 4.3 years of patient enrollment (December 1984 to April 1989), is being extended for 3 years (December 1988 to December 1991) to provide the time needed to accrue additional patients, aged between 1 1/2 and 10 years, with glomerular filtration rates of 20 to 75 ml/min/1.73 m2. The study design of randomization to two treatment arms (1,25-dihydroxyvitamin D vs dihydrotachysterol) requires a total of 108 patients with a minimum of 6 months of treatment to test the long-term effectiveness and safety of 1,25-dihydroxyvitamin D, an essential part of the therapeutic regimen for children with chronic renal insufficiency. The frequent longitudinal assessments of nutrition and growth in children with chronic renal insufficiency can better define the natural history of renal disease and its influence on growth. Similar data in the treatment period will define the impact of treatment with 1,25-dihydroxyvitamin D3 versus dihydrotachysterol on this natural history. Linear growth must be observed long enough (6 to 12 months minimum) to permit valid quantitation and comparison of the two vitamin D treatment arms, the multiple confounding variables that affect growth (e.g., steroid therapy, diabetes mellitus, prior vitamin D treatment) must be rigorously excluded or controlled, and the assignment of patients to the two groups must be random. These controls--sufficient study duration, sufficient patient numbers, and randomization--should eliminate extraneous sources of variation, including seasonal periodicity. This carefully developed, double-blind clinical trial with multiple participating centers and an effective organizational structure is coming close to achieving the goals of the study. An explosion of data regarding the natural history of chronic renal insufficiency and its treatment with vitamin D metabolites will be forthcoming at the conclusion of the study.

Data coordination and management in the Growth Failure in Children with Renal Diseases Study.

The DDC of the GFRD Study works closely with the Administrative Core and with all participating clinical centers to ensure the timely collection of accurate, reliable, and complete data. The development and maintenance of a data-base management system, including continuous monitoring of all data, represent primary responsibilities of the DCC. Coordination and communication tasks in the multicenter study have been challenging but rewarding. Proper planning and positive attitudes have enhanced the effectiveness of the DCC throughout this clinical trial.