Prevalence and correlates of sun protections with sunburn and vitamin D deficiency in sun-sensitive individuals.

BACKGROUND: Sun sensitivity is an inherent risk factor for skin cancer. Sun protection is important in sun-sensitive individuals to reduce sunburns for skin cancer prevention. However, concerns have arose regarding the possible impact of sun protection on vitamin D deficiency. OBJECTIVE: To examine the prevalence and correlates of sun-protective behaviours (staying in the shade, using sunscreen and wearing long sleeves) with sunburn and vitamin D deficiency in sun-sensitive individuals. METHODS: This was a cross-sectional study of 2390 US non-Hispanic white adults aged 20-59 years in the National Health and Nutrition Examination Survey 2011-2014. Sun sensitivity was defined as self-reported tendency to severe sunburn when exposed to the sun for half an hour after months of non-sun exposure, and single serum 25(OH)D levels less than 50 nmol/L was determined as vitamin D deficiency. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) using multivariable logistic regression taking into account the complex survey design. RESULTS: Sun-sensitive individuals had higher odds of frequently staying in the shade (aOR = 3.08; 95% CI 2.19-4.33) and using sunscreen (aOR = 1.93; 1.44-2.59) but not associated with sun exposure time (aOR = 0.91; 0.62-1.32). Yet, sun-sensitive individuals had significantly higher likelihood of sunburns (aOR = 1.93; 1.45-2.55), and no increased likelihood of vitamin D deficiency (aOR = 1.15; 0.84-1.58). Among sun-sensitive individuals, being younger, male and spending more time outdoors were associated with increased odds of sunburns and the risk of sunburn was reduced with frequently staying in the shade and engaging in multimodal sun protections. CONCLUSION: Sun-sensitive individuals more frequently used sun protection methods yet they still were significantly more likely to experience sunburns and the risk of vitamin D deficiency was not increased. Education on proper application of sunscreen combined with other sun-protective techniques is important to reduce sunburn in sun-sensitive populations.

Time-resolved contrast-enhanced MRA (TWIST) with gadofosveset trisodium in the classification of soft-tissue vascular anomalies in the head and neck in children following updated 2014 ISSVA classification: first report on systematic evaluation of MRI and TWIST in a cohort of 47 children.

AIM: To evaluate the relative accuracy of contrast-enhanced time-resolved angiography with interleaved stochastic trajectories versus conventional contrast-enhanced magnetic resonance imaging (MRI) following International Society for the Study of Vascular Anomalies updated 2014-based classification of soft-tissue vascular anomalies in the head and neck in children. MATERIALS AND METHODS: Time-resolved angiography with interleaved stochastic trajectories versus conventional contrast-enhanced MRI of children with diagnosis of soft-tissue vascular anomalies in the head and neck referred for MRI between 2008 and 2014 were retrospectively reviewed. Forty-seven children (0-18 years) were evaluated. Two paediatric neuroradiologists evaluated time-resolved MRA and conventional MRI in two different sessions (30 days apart). Blood-pool endovascular MRI contrast agent gadofosveset trisodium was used. RESULTS: The present cohort had the following diagnoses: infantile haemangioma (n=6), venous malformation (VM; n=23), lymphatic malformation (LM; n=16), arteriovenous malformation (AVM; n=2). Time-resolved MRA alone accurately classified 38/47 (81%) and conventional MRI 42/47 (89%), respectively. Although time-resolved MRA alone is slightly superior to conventional MRI alone for diagnosis of infantile haemangioma, conventional MRI is slightly better for diagnosis of venous and LMs. Neither time-resolved MRA nor conventional MRI was sufficient for accurate diagnosis of AVM in this cohort. Conventional MRI combined with time-resolved MRA accurately classified 44/47 cases (94%). CONCLUSION: Time-resolved MRA using gadofosveset trisodium can accurately classify soft-tissue vascular anomalies in the head and neck in children. The addition of time-resolved MRA to existing conventional MRI protocols provides haemodynamic information, assisting the diagnosis of vascular anomalies in the paediatric population at one-third of the dose of other MRI contrast agents.

Vitamin D, vitamin D binding protein gene polymorphisms, race and risk of incident stroke: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND AND PURPOSE: Low vitamin D levels, measured by serum 25-hydroxyvitamin D [25(OH)D], are associated with increased stroke risk. Less is known about whether this association differs by race or D binding protein (DBP) single nucleotide polymorphism (SNP) status. Our objective was to characterize the associations of and interactions between 25(OH)D levels and DBP SNPs with incident stroke. It was hypothesized that associations of low 25(OH)D with stroke risk would be stronger amongst persons with genotypes associated with higher DBP levels. METHODS: 25(OH)D was measured by mass spectroscopy in 12 158 participants in the Atherosclerosis Risk in Communities (ARIC) study (baseline 1990-1992, mean age 57 years, 57% female, 23% black) and they were followed through 2011 for adjudicated stroke events. Two DBP SNPs (rs7041, rs4588) were genotyped. Cox models were adjusted for demographic/behavioral/socioeconomic factors. RESULTS: During a median of 20 years follow-up, 804 incident strokes occurred. The lowest quintile of 25(OH)D (<17.2 ng/ml) was associated with higher stroke risk [hazard ratio (HR) 1.34 (1.06-1.71) versus highest quintile]; this association was similar by race (P interaction 0.60). There was weak evidence of increased risk of stroke amongst those with 25(OH)D < 17.2 ng/ml and either rs7041 TG/GG [HR = 1.29 (1.00-1.67)] versus TT genotype [HR = 1.19 (0.94-1.52)] (P interaction 0.28) or rs4588 CA/AA [HR = 1.37 (1.07-1.74)] versus CC genotype [HR = 1.14 (0.91-1.41)] (P interaction 0.11). CONCLUSIONS: Low 25(OH)D is a risk factor for stroke. Persons with low 25(OH)D who are genetically predisposed to high DBP (rs7041 G, rs4588 A alleles), who therefore have lower predicted bioavailable 25(OH)D, may be at greater risk for stroke, although our results were not conclusive and should be interpreted as hypothesis generating.

The Neonatal Pain, Agitation and Sedation Scale and the bedside nurse's assessment of neonates.

OBJECTIVE: To determine the reliability of an objective measure of pain, agitation and sedation using the Neonatal Pain, Agitation and Sedation Scale (N-PASS) compared with nursing bedside assessment. STUDY DESIGN: Neonates admitted in neonatal intensive care unit over a 6-month period were eligible. Pain and sedation were assessed with N-PASS, and a subjective questionnaire was administered to the bedside nurse. RESULT: A total of 218 neonates were eligible (median: gestational age 34.6 weeks, age at assessment 7 days). N-PASS pain score correlated significantly with both nurses' pain score (Spearman coefficient (r)=0.37; P<0.001) and agitation score (r=0.56; P<0.001). N-PASS sedation score correlated with nurses' sedation score (r=-0.39; P<0.001). Adjusting for gestational age, day of life, intrauterine drug exposure and use of high frequency ventilation only slightly attenuated the correlations (r=0.36, 0.55 and -0.31, respectively). CONCLUSION: The N-PASS captures nursing assessment of pain, agitation and sedation in this broad population and provides a quantitative assessment of subjective descriptions that often drives patient therapy.

Vitamin D and cognitive function and dementia risk in a biracial cohort: the ARIC Brain MRI Study.

BACKGROUND AND PURPOSE: Some recent studies in older, largely white populations suggest that vitamin D, measured by 25-hydroxyvitamin D [25(OH)D], is important for cognition, but such results may be affected by reverse causation. Measuring 25(OH)D in late middle age before poor cognition affects behavior may provide clearer results. METHODS: This was a prospective cohort analysis of 1652 participants (52% white, 48% black) in the Atherosclerosis Risk in Communities (ARIC) Brain MRI Study. 25(OH)D was measured from serum collected in 1993-1995. Cognition was measured by the delayed word recall test (DWRT), the digit symbol substitution test (DSST) and the word fluency test (WFT). Dementia hospitalization was defined by ICD-9 codes. Adjusted linear, logistic and Cox proportional hazards models were used. RESULTS: Mean age of participants was 62 years and 60% were female. Mean 25(OH)D was higher in whites than blacks (25.5 vs. 17.3 ng/ml, P < 0.001). Lower 25(OH)D was not associated with lower baseline scores or with greater DWRT, DSST or WFT decline over a median of 3 or 10 years of follow-up (P > 0.05). Over a median of 16.6 years, there were 145 incident hospitalized dementia cases. Although not statistically significant, lower levels of 25(OH)D were suggestive of an association with increased dementia risk [hazard ratio for lowest versus highest race-specific tertile: whites 1.32 (95% confidence interval 0.69, 2.55); blacks 1.53 (95% confidence interval 0.84, 2.79)]. CONCLUSIONS: In contrast to prior studies performed in older white populations, our study of late middle age white and black participants did not find significant associations between lower levels of 25(OH)D with lower cognitive test scores at baseline, change in scores over time or dementia risk.

Payment to healthy volunteers in clinical research: the research subject's perspective.

Although there is much discussion regarding the ethics of making payments to healthy volunteers for participating in clinical research, little data are available from the point of view of the volunteers as to what they would consider to be fair payment. The objectives of this study were to determine healthy volunteers' estimates of appropriate payments for participation in hypothetical clinical trials in order to explore the reasoning behind these estimates and to examine the association between volunteer demographics and payment expectations. Sixty participants with previous experience as healthy volunteers in research studies were presented with four hypothetical studies and interviewed about their impressions of burden and risks involved in the studies. They were also asked to estimate an appropriate payment to the volunteers for each of the studies. For each of the studies, the payment estimates made by the participants varied over a wide range. However, each individual tended to be consistent in estimate placement within this range. No demographic factor was significantly associated with the estimated study payment. Subjects frequently mentioned risk and logistical burden as factors that should determine payment levels. Healthy volunteer subjects appear to have individualized yet consistent methods of arriving at estimates of payments for participating in clinical studies. These estimates are based on each subject's perception of study burden and associated risk.

Balancing justice and autonomy in clinical research with healthy volunteers.

In clinical research, ethics review generally first examines whether study risks are reasonable in light of benefits provided. Through informed consent, then, prospective subjects consider whether the risk/benefit balance and procedures are reasonable for them. Unique ethics issues emerge in clinical research with healthy volunteers. Certain types of studies only recruit healthy volunteers as participants. Phase 1 studies, for example, including first time in human studies of investigational drugs and vaccines, generally are conducted in healthy volunteers. Although such research carries inherent and often unknown risks, healthy subjects provide the most efficient target population in which to conduct such research, as these volunteers generally are free of concurrent diseases or medications that could confound interpretation of toxicity. Other studies enrolling healthy volunteers often are simply looking for the most scientifically sound population for the study of normal human physiology.

APOE genotype and survival in men and women with Alzheimer's disease.

BACKGROUND: The epsilon 4 allele of the APOE gene (APOE) is more frequent in patients with AD than in the general population, but studies are inconclusive as to whether it affects rate of progression or survival. Because survival in AD is generally longer in women than in men, the authors investigated whether APOE affects 10-year survival equally in men and women. METHODS: APOE testing was performed on 125 patients with probable AD enrolled in the Johns Hopkins AD Research Center between November 1984 and March 1987. The 39 men and 86 women were followed at 6-month intervals until censoring (by death or withdrawal from the study) or March 1997. Patients were dichotomized into those with and those without at least one epsilon 4 allele. For each sex, a Cox proportional hazards regression, allowing for delayed entry and covarying for age at onset, was used to examine the effect of epsilon 4 on survival. RESULTS: All patients who died during the study period and had autopsy (n = 92) were found to have definite AD. Average survival from disease onset did not differ by sex (12.1 years in men; 12.3 years in women). In neither sex were differences found between epsilon 4-positive and epsilon 4-negative subgroups in education, duration of AD at entry, or severity of dementia. However, in both sexes the epsilon 4-positive subgroup was approximately 3 years older at onset of AD and at entry to the study than the epsilon 4-negative subgroup. Adjusting for age at onset, the presence of an epsilon 4 allele significantly increased the relative risk of death only for men (RR = 2.69; 95% CI = 1.23 to 5.87). CONCLUSIONS: In this sample of mostly white, well-educated research participants with AD, the APOE epsilon 4 allele was associated with shorter survival in men but not in women.

Olfactory mucosa ultrastructure in the short-tailed shrews, Blarina brevicauda and Blarina carolinensis.

The olfactory mucosae of the northern short-tailed shrew, Blarina brevicauda, and the southern short-tailed shrew, Blarina carolinensis, were examined by light and electron microscopy. A well-developed olfactory epithelium was observed that included all of the cells necessary to provide for a sensitive olfactory system, suggesting that olfaction plays a major role in the behavior of these animals. There were no significant differences between the olfactory mucosae of these two species. The general features of the olfactory epithelium in these shrews were similar to those reported for several other macrosmatic mammals. A new type of supporting cell, called the light supporting cell, was observed in these shrews. The light supporting cell cytoplasm exhibited very little staining by light microscopy and had low electron density by transmission electron microscopy compared to that of the more common dark supporting cell. The light supporting cell had a convex apical surface with microvilli and lacked the large amounts of smooth endoplasmic reticulum (SER) typical of the apical cytoplasm of the dark supporting cell. In the lamina propria of the mucosa, the Bowman's glands consisted of two cell types, one with electron-lucent, alcian blue-positive granules, and the other with electron-dense PAS-positive granules. The cell with electron-lucent granules contained large amounts of SER and small clumps of rough ER. The cells with electron-dense granules had large amounts of RER and little SER.

Test characteristics of immunofluorescence and ELISA tests in 856 consecutive patients with possible ANCA-associated conditions.

OBJECTIVE: To examine the test characteristics of immunofluorescence (IF) and enzyme-linked immunosorbent assays (ELISA) in a consecutive series of patients under evaluation for anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). METHODS: Using stored sera, we performed a cross-sectional study on 856 consecutive patients tested prospectively for ANCA by IF, Based on guidelines from the 1994 Chapel Hill Consensus Conference (CHCC), we determined each patient's underlying diagnosis by a medical records review without regard to their ANCA status (the CHCC guidelines do not require ANCA as a prerequisite for diagnosis). We grouped patients with forms of vasculitis commonly associated with ANCA into one of 4 types of AAV: Wegener's granulomatosis (n = 45), microscopic polyangiitis (n = 12), Churg-Strauss syndrome (n = 4), and pauci-immune glomerulonephritis (n = 8). We also classified patients without clinical evidence of AAV (92% of all patients tested) into 5 predefined categories of disease (including "other") and an additional category for no identifiable disease. In a blinded fashion, we then performed ELISAs on the stored serum for antibodies to proteinase-3 (PR3) and myeloperoxidase (MPO) and calculated the test characteristics for both ANCA assay techniques. RESULTS: Sixty-nine of the 856 patients (8.1%) had clinical diagnoses of AAV based on CHCC guidelines. The positive predictive value (PPV) of ELISA for AAV was superior to that of IF, 83% versus 45%. For patients with both positive IF tests and positive ELISA tests, the PPV increased to 88%. Both IF and ELISA had high negative predictive values (97% and 96%, respectively). Positive ELISA tests were associated with higher likelihood ratios (LR) than IF (54.2 [95% CI = 26.3, 111.5] versus 9.4 [95% CI = 6.9, 12.7]). The LR of both a positive IF and a positive ELISA was 82.1 (95% CI = 33.3, 202.5). CONCLUSIONS: Compared with IF, an ELISA test fo ANCA was associated with a substantially higher PPV and LR for AAV. This fact, combined with the greater sensitivity of IF, suggests that an effective testing strategy is to perform ELISA tests only on samples that are positive for ANCA by IF.

Lack of relation between race and cognitive test performance in Alzheimer's disease.

This study evaluated cognitive test performance in African-American and European-American Alzheimer's disease patients with equivalent years of education. Group differences were negligible on a variety of memory, language, and attentional measures, including several widely used neuropsychological tests. Differences between racial groups observed in earlier studies may have stemmed, in part, from differences in education, which may itself serve as a proxy for other potentially important sociologic and health variables.

Electron microscopic investigation of the effects of diabetes mellitus on the Achilles tendon.

Fine structural changes in the Achilles tendons of patients with long-term diabetes mellitus were investigated. All patients had clinical and electrophysiological evidence of diabetic neuropathy and had ulceration and/or Charcot neuroarthropathy. Several differences between tendons of diabetic (n = 12) and nondiabetic (n = 5) individuals were observed by electron microscopy. In diabetics, these differences included increased packing density of collagen fibrils, decreases in fibrillar diameter, and abnormal fibril morphology. In one diabetic patient, individual collagen fibrils were tightly apposed so that many areas of tendon appeared as a single mass of closely adhering fibrillae. In addition, foci in which collagen fibrils appeared twisted, curved, overlapping and otherwise highly disorganized were common in specimens from most patients (11 of 12). These morphologic abnormalities in the Achilles tendons of diabetics appear to reflect a poorly known process of structural reorganization that may be the result of nonenzymatic glycation expressed over many years. Such structural changes could contribute to the tightening of the Achilles tendor a phenomenon consistent with clinical observations of extreme shortening of the Achilles tendon-gastrocnemius-soleus complex common in advanced diabetic neuropaths. In patients with diabetic neuropathy, tendon shortening causes severe equinus that may precipitate serious ulceration, stress fractures, and Charcot collapse of the foot. However, in nondiabetics, the fine structure of the Achilles tendon appears normal, consistent with the finding that the ultrastructural changes result from diabetes rather than neuropathy.

Predicting rate of cognitive decline in probable Alzheimer's disease.

Recent attempts to identify predictors of rate of decline in Alzheimer's disease (AD) have been extremely variable in choice of outcome variables, predictor variables tested, timing of assessments, and statistical approaches. In this study, a random effects regression model was applied to seek predictors of decline on the Mini-Mental State Exam in 132 patients with probable AD reassessed every 6 months for up to 7.5 years. Potential predictor variables at baseline were of three types: patients characteristics, clinical variables, and cognitive performances. The final multivariate analysis indicated that the following characteristics predicted more rapid cognitive decline: more education, history of dementia in a first degree relative, non-right handedness, better performances of Boston Naming Test, Gollin Incomplete Figures Test, and Benton Visual Retention Test-Delay, and worse performances on Responsive Naming Test, WAIS-R Block Design, and Benton Visual Retention Test-Copy.

Apolipoprotein E genotype and rate of decline in probable Alzheimer's disease.

BACKGROUND: The risk of Alzheimer's disease (AD) appears to increase, and the age at onset to decrease, with the number of epsilon 4 alleles. If this relationship is due to increased rate of pathophysiological change, the presence of epsilon 4 would be expected to influence progression of disease, predicting a more rapid decline with increasing number of epsilon 4 alleles. OBJECTIVE: To determine if the frequency of the epsilon 4 allele of the apolipoprotein E (ApoE) gene affects the rate of clinical progression in AD. SETTING: Alzheimer's Disease Research Center. SUBJECTS: One hundred one subjects meeting criteria of the National Institute of Neurological Disorders and Stroke for probable AD or of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) for definite AD; 78 of these subjects met the additional criterion of having a Mini-Mental State Examination score of at least 10 for analysis of rate of decline. MEASUREMENTS: The subjects' characteristics and neuropsychological battery, including the Mini-Mental state Examination, Spatial Delayed Recognition Span, Boston Naming Test, Category Fluency Test, and the Physical Capacity Subscale of the Psychogeriatric Dependency Rating Scale. DESIGN: The subjects were followed up longitudinally for approximately one decade. Medical histories were taken and physical and neurologic examinations and neuropsychological testing were performed every 6 months. Three and a half years of data were available for most tests and 5.5 for the Psychogeriatric Dependency Rating Scale; thereafter, patients were no longer testable. A general linear model analysis of variance was used to assess the influence of ApoE on demographic characteristics and baseline performances on neuropsychological measures. A random-effects regression model was used to predict change over time associated with presence of epsilon 4 on clinical and cognitive measures. RESULTS: The age at onset was greatest for the epsilon 4-heterozygous subjects and least for the epsilon 4-negative subjects. The heterozygous subjects declined more rapidly on the Mini-Mental State Examination and the Category Fluency Test than the subjects without the epsilon 4 allele or with epsilon homozygosity. The homozygous subjects declined faster on only one subscale: the Physical Capacity subscale of the Psychogeriatric Dependency Rating Scale. Covarying for age at onset did not affect the results. CONCLUSIONS: The ApoE genotype does not strongly influence the rate of decline in AD, implying that epsilon 4 might predispose to the development of the disease without accelerating its pathogenesis or progression. The effects of epsilon 4 on both age at onset and rate of decline need to be further investigated.

Nonsteroidal anti-inflammatory drugs in Alzheimer's disease.

We reviewed the records of 210 patients in the Johns Hopkins Alzheimer's Disease Research Center to evaluate the role of nonsteroidal anti-inflammatory drugs (NSAIDs) on clinical features and progression of the disease. We compared patients taking NSAIDs or aspirin on a daily basis (N = 32) to non-NSAID patients (N = 177) on clinical, cognitive, and psychiatric measures. The NSAID group had a significantly shorter duration of illness at study entry. Even after controlling for this difference, the NSAID group performed better on the Mini-Mental State Examination, Boston Naming Test, and the delayed condition of the Benton Visual Retention Test. Furthermore, analysis of longitudinal changes over 1 year revealed less decline among NSAID patients than among non-NSAID patients on measures of verbal fluency, spatial recognition, and orientation. These findings support other recent studies suggesting that NSAIDs may serve a protective role in Alzheimer's disease.

Fine structure of the submandibular salivary gland of the venomous short-tailed shrew, Blarina brevicauda Say (Insectivora: Soricidae).

Adult male short-tailed shrews, Blarina brevicauda, (Insectivora: Soricidae) were trapped in Virginia and Pennsylvania, anesthetized, and perfused via the left ventricle of the heart with fixative. The submandibular glands were dissected free and prepared for transmission electron microscopy. The lobular, compound tubuloacinar glands had secretory endpieces consisting of seromucous acini and serous tubules connected to intercalated ducts, granular ducts, striated ducts, and excretory ducts. The general cytology of the submandibular gland of Blarina shared morphological characters with individuals in several other mammalian orders and yet differed in many ways from another Insectivore, the European hedgehog, Erinaceus europaeus.

Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue.

Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity was localized by electron microscopic enzyme cytochemistry in cortex from Alzheimer brains and brains from non-demented cases. In the tangle-rich medial temporal cortex of the Alzheimer brain, most of the neuronal AChE was associated with neurofibrillary tangles. These structures also contained BChE activity. In normal neurons AChE activity was found in the rough endoplasmic reticulum, nuclear envelope and Golgi apparatus. Little BChE activity was noted in normal cortex. In neuritic plaques, AChE and BChE activity was associated mostly with the amyloid, but also with the neuritic component.

Reinnervation of peripheral nerve grafts by spinal cord fibres tested by transcranial brain stimulation.

A scheme for surgery in patients with avulsed roots is represented by a rat model whose left sciatic nerve was grafted upon the right sciatic nerve, the proximal end of the graft being introduced into the spinal cord white matter. Transcranial stimulation, EMG recording, HRP and histological studies proved that the communication between the brain and the denervated muscles may be reestablished via the motoneurons, through the graft, bypassing the motor roots. Behavioral techniques were developed and will be tested in the future. The possibility of using neurotrophic drugs will be considered.