Receiver Operating Characteristic (ROC) to Determine Cut-Off Points of Biomarkers in Lung Cancer Patients

The role of biomarkers in disease prognosis continues to be an important investigation in many cancer studies. In order for these biomarkers to have practical application in clinical decision making regarding patient treatment and follow-up, it is common to dichotomize patients into those with low vs. high expression levels. In this study, receiver operating characteristic (ROC) curves, area under the curve (AUC) of the ROC, sensitivity, specificity, as well as likelihood ratios were calculated to determine levels of growth factor biomarkers that best differentiate lung cancer cases versus control subjects. Selected cut-off points for p185^erbB-2 and EGFR membrane appear to have good discriminating power to differentiate control tissues versus uninvolved tissues from patients with lung cancer (AUC = 89% and 90%, respectively); while AUC increased to at least 90% for selected cut-off points for p185^erbB-2 membrane, EGFR membrane, and FASE when comparing between control versus carcinoma tissues from lung cancer cases. Using data from control subjects compared to patients with lung cancer, we presented a simple and intuitive approach to determine dichotomized levels of biomarkers and validated the value of these biomarkers as surrogate endpoints for cancer outcome.     

Dengue infections during pregnancy: a case series from Sri Lanka and review of the literature.

BACKGROUND: Dengue is a major public health problem in several countries. Few reports document presentations and outcomes of dengue during pregnancy. In many endemic countries as the average age of getting dengue infections is shifting upwards, dengue in pregnancy is likely to be encountered more frequently. Patterns of dengue in patients from different regions are needed if we are to draft evidence based management guidelines. OBJECTIVES: To document clinical and laboratory findings in a cohort of hospitalised patients with dengue during pregnancy in Sri Lanka and compare their presentation and outcomes with previously published cases. STUDY DESIGN: Clinical, laboratory, maternal and fetal outcomes and demographic information were collected from patients with confirmed dengue infections during pregnancy treated in a Maternity Hospital in Sri Lanka from 1 January 2000 to 30 June 2004. The Medline database was searched to identify reports relating to dengue infection during pregnancy since 1965. RESULTS: Twenty-six patients [mean (S.D.) age: 29 (4.2) years] were studied. One (3.8%), 2 (7.7%) and 20 (77%) presented in the first, second and third trimesters of pregnancy, and 3 (11.5%) in the immediate post-partum period. Seventeen (65.3%) had primary and nine (34.7%) secondary dengue infections. Ten (38.5%) had DF, 6 (23.1%): DHF grade I and 10 (38.5%): DHF grade II. Five (19.2%) and three (11.5%) patients who first presented with cough/breathlessness or vaginal bleeding, were initially managed as having a pulmonary embolism or a primary obstetric cause for their vaginal bleeding. Bradycardia was noted in three of the four patients who had a cardiac arrhythmia. Seven (26.9%) needed admission to an ICU. Raised AST and ALT levels were seen in 81.2% and 43.7% of 16 patients in whom liver function tests results were available. No fetal malformations were seen in any of the babies born. The single patient who developed DHF in the first trimester had an abortion while having acute symptoms of dengue. CONCLUSIONS: Awareness of clinical and laboratory manifestations of dengue in pregnancy should allow its early recognition and institution of appropriate treatment. Reports on dengue in pregnancy from different regions should allow more evidence-based guidelines to be formulated for optimum evaluation and care of such patients. Our data contributes towards this goal.     

Associations between two common variants C677T and A1298C in the methylenetetrahydrofolate reductase gene and measures of folate metabolism and DNA stability (strand breaks, misincorporated uracil, and DNA methylation status) in human lymphocytes in vivo.

OBJECTIVE: Homozygosity for variants of the methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased risk for colorectal cancer. We have investigated the relationships between two variants of the MTHFR gene (C677T and A1298C) and blood folate, homocysteine, and genomic stability (strand breakage, misincorporated uracil, and global cytosine methylation in lymphocytes) in a study of 199 subjects. RESULTS: The frequencies of homozygosity for the C677T and A1298C variants of the MTHFR gene were 12.6% and 14.6%, respectively. Plasma homocysteine, folate, vitamin B12, 5-methyltetrahydrofolate, and RBC folate were determined in the C677T genotypes. Plasma folate was significantly lower (P < 0.001) in the homozygous variants (6.7 +/- 0.6 ng/mL) compared with wild-types (8.8 +/- 0.4 ng/mL) and heterozygotes (9.1 +/- 0.5 ng/mL). Homocysteine was significantly higher (P < 0.05) in homozygous variants (13.2 +/- 1.1 micromol/L) compared with homozygous subjects (10.9 +/- 0.4 micromol/L). Homozygous variants had significantly lower (P < 0.05) RBC folate (84.7 +/- 6.3 ng/mL) compared with wild-types (112.2 +/- 5.2 ng/mL) and heterozygous individuals (125.1 +/- 6.6 ng/mL). No significant difference in RBC folate was observed between wild-types and heterozygotes. The A1298C variant did not influence plasma homocysteine, folate, 5-methyltetrahydrofolate, vitamin B12, or RBC folate. Lymphocyte DNA stability biomarkers (strand breaks, misincorporated uracil, and global DNA methylation) were similar for all MTHFR C677T or A1298C variants. CONCLUSION: Data from this study do not support the hypothesis that polymorphisms in the MTHFR gene increase DNA stability by sequestering 5,10-methylenetetrahydrofolate for thymidine synthesis and reducing uracil misincorporation into DNA.     

Bronchial asthma with ABPA presenting as PTE

Allergic bronchopulmonary aspergillosis (ABPA), as a complication of asthma, is rare in children. The persistent and poorly-controlled asthma leading to cor pulmonale is not uncommon in adults but rarely described in the pediatric age group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo-embolism and cor pulmonale. To the best of our knowledge, such association has never been reported in the pediatric age group.     

Evidence summaries and recommendations from the international evidence‐based guideline for the assessment and management of polycystic ovary syndrome: Lifestyle management

Lifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first‐line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence‐based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence‐based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence‐based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first‐line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers.     

Endonuclease VIII-like 1 (NEIL1) promotes short-term spatial memory retention and protects from ischemic stroke-induced brain dysfunction and death in mice

Recent findings suggest that neurons can efficiently repair oxidatively damaged DNA, and that both DNA damage and repair are enhanced by activation of excitatory glutamate receptors. However, in pathological conditions such as ischemic stroke, excessive DNA damage can trigger the death of neurons. Oxidative DNA damage is mainly repaired by base excision repair (BER), a process initiated by DNA glycosylases that recognize and remove damaged DNA bases. Endonuclease VIII-like 1 (NEIL1) is a DNA glycosylase that recognizes a broad range of oxidative lesions. Here, we show that mice lacking NEIL1 exhibit impaired memory retention in a water maze test, but no abnormalities in tests of motor performance, anxiety, or fear conditioning. NEIL1 deficiency results in increased brain damage and a defective functional outcome in a focal ischemia/reperfusion model of stroke. The incision capacity on a 5-hydroxyuracil-containing bubble substrate was lower in the ipsilateral side of ischemic brains and in the mitochondrial lysates of unstressed old NEIL1-deficient mice. These results indicate that NEIL1 plays an important role in learning and memory and in protection of neurons against ischemic injury.     

Simplified Technique for Orbital Prosthesis Fabrication: A Clinical Report

Loss of orbital content can cause functional impairment, disfigurement of the face, and psychological distress. Rehabilitation of an orbital defect is a complex task, and if reconstruction by plastic surgery is not possible or not desired by the patient, the defect can be rehabilitated by an orbital prosthesis. The prosthetic rehabilitation in such cases depends on the precisely retained, user‐friendly removable maxillofacial prosthesis. Many times, making an impression of the orbital area with an accurate record of surface details can be a difficult procedure. The critical areas are making a facial moulage, mold preparation, and attaching the retention device, particularly when eyeglass frames are used. This case focuses on these hindrance factors. A simple basket was used for the impression tray to obtain the facial moulage. A putty mold was used, and attachment of the prosthesis to a retention device was accomplished with positional distance. This method proves to be an economical and simple way of making an orbital prosthesis.