Mechanism of UV-related carcinogenesis and its contribution to nevi/melanoma

Melanoma consists 4-5 % of all skin cancers, but it contributes to 71-80 % of skin cancers deaths. UV light affects cell and tissue homeostasis due to its damaging effects on DNA integrity and modification of expression of a plethora of genes. DNA repair systems protect cells from UV-induced lesions. Several animal models of melanoma have been developed (Xiphophorus, Opossum Monodelphis domestica, mouse models and human skin engrafts into other animals). This review discusses possible links between UV and genes significantly related to melanoma but does not discuss melanoma genetics. These include oncogenes, tumor suppressor genes, genes related to melanocyte-keratinocyte and melanocyte-matrix interaction, growth factors and their receptors, CRH, ACTH, α-MSH, glucocorticoids, ID1, NF-kappaB and vitamin D3.     

Screening for diabetes: sensitivity and positive predictive value of risk factor total.

OBJECTIVE: Screening for diabetes is recommended for individuals > or =45 years of age, or earlier if they manifest > or = one specific risk factors. This study examined the sensitivity and positive predictive value (PPV) of risk factor total for identifying individuals with diabetes and prediabetes. DESIGN: Subjects were interviewed to assess the presence of risk factors. Fasting plasma glucose levels were obtained. SETTING: The study occurred at a health fair in Greensburg, PA. PATIENTS: Six hundred sixty-one Caucasians between the ages of 19 and 100. RESULTS: Using the criterion of screening individuals with > or = one risk factors detected 100% of both diabetics and prediabetics. This dropped to 91.2% when screening individuals with > or = two factors. The PPV of the risk factor total was poor (80% of individuals with a total of four factors were not diabetic). The ability of the risk factor total to predict individuals with impaired glucose metabolism (prediabetics + diabetics) was considerably better, and increased almost linearly with the risk factor total. Of the subjects with normal glucose values, the mean glucose increased as the risk factor total increased. CONCLUSION: While the sensitivity of using > one risk factor as an algorithm to screen is 100% for identifying diabetics, the PPV of risk factor analysis for identifying diabetics is poor. The same algorithm works well to identify at-risk individuals, presumably allowing early intervention and education.     

Changes over 6-months in health-related quality of life in a matched sample of hispanics and non-hispanics with heart failure

Hispanics are a growing ethnic minority in the United States and one at significant risk for heart failure. Health-related quality of life (HRQL) is poor in individuals with heart failure, especially during and immediately following hospitalization. No prior research into the HRQL of Hispanics with heart failure was located. A sample of 80 individuals with heart failure, evenly divided by primary language and matched on functional status using the New York Heart Association classification system and age, was studied for 6 months following hospital discharge. Data on HRQL were collected using Spanish and English versions of the Minnesota Living with Heart Failure Questionnaire. Scores improved over time in both groups but significantly more so in the Hispanics when compared to the non-Hispanics. Group differences in HRQL could not be explained by demographics, clinical characteristics, treatment received, perceived support, or instrument response characteristics. Further exploration of this naturally occurring phenomenon may provide insight into how HRQL can be improved in the general heart failure population.     

Prevalence of post-traumatic stress disorder symptoms in orofacial pain patients.

OBJECTIVE: There is a high comorbidity between symptoms of post-traumatic stress disorder (PTSD) and chronic pain incidence. The objective of this investigation was to determine the prevalence of PTSD symptoms in chronic orofacial pain patients. STUDY DESIGN: The study included 1478 adult patients (mean age 36.4 +/- 12.7 years) with primary diagnoses of masticatory/cervical muscle pain or temporomandibular joint pain. Patients completed a battery of psychometric questionnaires including a screening for PTSD symptoms. The sample was divided into a PTSD-positive group (n=218, 15%) a PTSD-negative group (n=551, 37%), and a no-stressor group (n=709, 48%) according to stressor incidence and symptom severity. RESULTS: The current prevalence of PTSD symptomatology was considerably higher than that reported in surveys from the general population. Patients in the PTSD-positive symptom group reported significantly higher psychological distress, sleep dysfunction, and pain severity compared to patients in the other groups. Psychological distress as measured by the SCL-90-R reached clinically significant levels only in those patients with PTSD symptomatology. CONCLUSIONS: The results of this study performed at a tertiary care center suggest that TMD patients without PTSD symptomatology show low levels of psychological distress, if any. Clinically significant levels of psychological distress are likely indicators for PTSD. PTSD screening should be included as part of a routine psychometric test battery in TMD patients.     

Variations in human corneal endothelial cell morphology and permeability to fluorescein with age

Fluorophotometry with topically applied fluorescein and endothelial cell photography were performed on 80 normal subjects (age 5-79 yr). Variations in endothelial cell morphology and function, flow of aqueous humor, and intraocular pressure were recorded. The mean endothelial cell size was 332.3 +/- 46.3 micron 2. A 28% increase in endothelial cell size was measured over the eight decades (r = 0.53, P less than 0.001). The coefficient of variation of cell size also increased with age (r = 0.41, P less than 0.001). The percentage of hexagonal endothelial cells decreased by 14% (r = -0.48, P less than 0.001), while the percentage of pentagonal and heptagonal cells increased by 50% (r = 0.44, P less than 0.001) and 40% (r = 0.33, P less than 0.002), respectively, with age. The mean endothelial permeability to fluorescein was 4.03 +/- 0.63 x 10(-4) cm min-1. A 23% increase in endothelial permeability with age was observed (r = 0.44, P less than 0.001). No change in central corneal thickness or endothelial pump rate was found. Flow of aqueous humor remained stable with age, despite a 25% increase in intraocular pressure (r = 0.50, P less than 0.001). Polarization of fluorescence of fluorescein in the corneal stroma decreased with age (r = -0.46, P less than 0.001). We conclude that with age the human corneal endothelium becomes morphologically less regular and may become more permeable to fluorescein.     

Melatonin receptors and signal transduction during development in Siberian hamsters (Phodopus sungorus).

Maternal melatonin communicates daylength information to the fetus in Siberian hamsters. Fetal sensitivity to melatonin declines near birth. In this report, we describe melatonin receptor distribution and a second messenger response to melatonin in Siberian hamsters during the perinatal period. The sites of high-affinity 2-[125I]iodomelatonin ([125I]MEL) binding were generally similar throughout the perinatal period. The non-hydrolyzable GTP analog, guanosine-5'-O-(3-thiotriphosphate) (100 microM) inhibited [125I]MEL binding at each age, suggesting the melatonin receptors are associated with guanine nucleotide binding proteins (G proteins). Furthermore, melatonin (10 nM) inhibited forskolin-stimulated cAMP accumulation in median eminence/pars tuberalis (ME/PT) explants as early as 4 days before birth, when sensitivity to melatonin in vivo is high. The cAMP regulatory system appeared disrupted on the day of birth, in that forskolin (10 microM) stimulation of cAMP accumulation was reduced, and melatonin did not inhibit cAMP accumulation stimulated by forskolin. A higher forskolin dose (100 microM) elevated cAMP levels more clearly on the day of birth, and melatonin inhibited forskolin-stimulated cAMP accumulation. These results suggest that the decreased physiological responsiveness to melatonin at the end of gestation may be due to alterations in the cAMP regulatory system.