Poor health among smokers obtaining colonoscopy screening: making the case for cessation intervention.

OBJECTIVES: Assess differences in perceived health status among individuals receiving colonoscopy screening based on smoking status. STUDY DESIGN: Cross-sectional data were collected as part of a larger study investigating whether verbal and non-verbal communication and behaviors of gastroenterologists and nurses. METHOD: Data for this study were collected between 2011 and 2013 among receiving colonoscopy screenings. Data were collected as part of a study assessing patients (n = 1785) undergoing colonoscopy screenings about their expectations, concerns, understanding of the procedure, and perceived health status. Differences between current, former and never smokers were analyzed using a one-way between subjects ANOVA, with a Scheffe post hoc. RESULTS: Post hoc analyses revealed that current smokers were significantly different from former or never smokers on the following variables: days their physical health was not good, days their mental health was not good, days health influenced their activities, days pain influenced their ability to perform activities, perceived general health, and current anxiety. CONCLUSION: This study looked at perceived health among individuals receiving colonoscopy screening by on smoking status, a relevant population based on the recent Surgeon Generals link. Former smokers reported similar health status across all variables as never smokers, suggesting the effect of quitting smoking on self-perceived health. With this link, tailored smoking cessation messages to smokers receiving colonoscopy screenings may be an excellent vantage point for a smoking cessation intervention.

Art therapy masks reflect emotional changes in military personnel with PTSS.

Among disabling post-traumatic stress symptoms (PTSS) are irritability, aggressive behavior, distressing memories and general impaired cognition and negative mood. Art therapy interventions, including mask-making, can potentially alleviate these symptoms. We tested the hypothesis that art conveys emotions and predicted that blinded viewers would be able to perceive changes in theoretically derived emotional profiles expressed in art made by military personnel with PTSS from the onset to the end of therapy. Five service members and veterans exhibiting PTSS were enrolled in an 8-session art therapy protocol, during which they artistically transformed papier-mâché masks at the beginning and end of the protocol. We found that blinded viewers without knowledge of the masks' creation stage (onset or end of therapy) read initial masks as conveying more negative emotions (e.g., angry, upset, and challenged) and later masks as conveying more positive emotions (calm and pleasure). Based on the assessments from the blinded evaluators, we infer the emotional transition experienced by the participants was expressed in the masks. In an exploratory arm of the study, we also found that viewers were better able to empathize with the negative emotions experienced by participants with PTSS when asked to explicitly take their perspective.

Association of whole mtDNA, an NADPH G11914A variant, and haplogroups with high physical performance in an elite military troop.

Physical performance is a multifactorial and complex trait influenced by environmental and hereditary factors. Environmental factors alone have been insufficient to characterize all outstanding phenotypes. Recent advances in genomic technologies have enabled the investigation of whole nuclear and mitochondrial genome sequences, increasing our ability to understand interindividual variability in physical performance. Our objective was to evaluate the association of mitochondrial polymorphic loci with physical performance in Brazilian elite military personnel. Eighty-eight male military personnel who participated in the Command Actions Course of the Army were selected. Total DNA was obtained from blood samples and a complete mitochondrial genome (mtDNA) was sequenced using Illumina MiSeq platform. Twenty-nine subjects completed the training program (FINISHED, 'F'), and fifty-nine failed to complete (NOT_FINISHED, 'NF'). The mtDNA from NF was slightly more similar to genomes from African countries frequently related to endurance level. Twenty-two distinct mtDNA haplogroups were identified corroborating the intense genetic admixture of the Brazilian population, but their distribution was similar between the two groups (FST=0.0009). Of 745 polymorphisms detected in the mtDNA, the position G11914A within the NADPH gene component of the electron transport chain, was statistically different between F and NF groups (P=0.011; OR: 4.286; 95%CI: 1.198-16.719), with a higher frequency of the G allele in group F individuals). The high performance of military personnel may be mediated by performance-related genomic traits. Thus, mitochondrial genetic markers such as the ND4 gene may play an important role on physical performance variability.

"The devil's in the detail": Release of an expanded, enhanced and dynamically revised forensic STR Sequence Guide.

The STR sequence template file published in 2016 as part of the considerations from the DNA Commission of the International Society for Forensic Genetics on minimal STR sequence nomenclature requirements, has been comprehensively revised and audited using the latest GRCh38 genome assembly. The list of forensic STRs characterized was expanded by including supplementary autosomal, X- and Y-chromosome microsatellites in less common use for routine DNA profiling, but some likely to be adopted in future massively parallel sequencing (MPS) STR panels. We outline several aspects of sequence alignment and annotation that required care and attention to detail when comparing sequences to GRCh37 and GRCh38 assemblies, as well as the necessary matching of MPS-based allele descriptions to previously established repeat region structures described in initial sequencing studies of the less well known forensic STRs. The revised sequence guide is now available in a dynamically updated FTP format from the STRidER website with a date-stamped change log to allow users to explore their own MPS data with the most up-to-date forensic STR sequence information compiled in a simple guide.

D5S2500 is an ambiguously characterized STR: Identification and description of forensic microsatellites in the genomics age.

In the process of establishing short tandem repeat (STR) sequence variant nomenclature guidelines in anticipation of expanded forensic multiplexes for massively parallel sequencing (MPS), it was discovered that the STR D5S2500 has multiple positions and genomic characteristics reported. This ambiguity is because the marker named D5S2500 consists of two different microsatellites forming separate components in the capillary electrophoresis multiplexes of Qiagen's HDplex (Hilden, Germany) and AGCU ScienTech's non-CODIS STR 21plex (Wuxi, Jiangsu, China). This study outlines the genomic details used to identify each microsatellite and reveals the D5S2500 marker in HDplex has the correctly assigned STR name, while the D5S2500 marker in the AGCU 21plex, closely positioned a further 1643 nucleotides in the human reference sequence, is an unnamed microsatellite. The fact that the D5S2500 marker has existed as two distinct STR loci undetected for almost ten years, even with reported discordant genotypes for the standard control DNA, underlines the need for careful scrutiny of the genomic properties of forensic STRs, as they become adapted for sequence analysis with MPS systems. We make the recommendation that precise chromosome location data must be reported for any forensic marker under development but not in common use, so that the genomic characteristics of the locus are validated to the same level of accuracy as its allelic variation and forensic performance. To clearly differentiate each microsatellite, we propose the name D5S2800 be used to identify the Chromosome-5 STR in the AGCU 21plex.

Association of whole mtDNA, an NADPH G11914A variant, and haplogroups with high physical performance in an elite military troop

Physical performance is a multifactorial and complex trait influenced by environmental and hereditary factors. Environmental factors alone have been insufficient to characterize all outstanding phenotypes. Recent advances in genomic technologies have enabled the investigation of whole nuclear and mitochondrial genome sequences, increasing our ability to understand interindividual variability in physical performance. Our objective was to evaluate the association of mitochondrial polymorphic loci with physical performance in Brazilian elite military personnel. Eighty-eight male military personnel who participated in the Command Actions Course of the Army were selected. Total DNA was obtained from blood samples and a complete mitochondrial genome (mtDNA) was sequenced using Illumina MiSeq platform. Twenty-nine subjects completed the training program (FINISHED, 'F'), and fifty-nine failed to complete (NOT_FINISHED, 'NF'). The mtDNA from NF was slightly more similar to genomes from African countries frequently related to endurance level. Twenty-two distinct mtDNA haplogroups were identified corroborating the intense genetic admixture of the Brazilian population, but their distribution was similar between the two groups (FST=0.0009). Of 745 polymorphisms detected in the mtDNA, the position G11914A within the NADPH gene component of the electron transport chain, was statistically different between F and NF groups (P=0.011; OR: 4.286; 95%CI: 1.198-16.719), with a higher frequency of the G allele in group F individuals). The high performance of military personnel may be mediated by performance-related genomic traits. Thus, mitochondrial genetic markers such as the ND4 gene may play an important role on physical performance variability.

Isoallele frequencies in very large populations.

The frequencies of electrophoretically distinguishable allelic forms of enzymes may be very different from the corresponding frequencies of structurally distinct forms, because many sequence variants may have identical electrophoretic charge. In large populations such frequencies will be determined largely by the number of amino acid sites that are free to vary. The number of distinguishable electrophoretic variants will remain fairly small. Beyond some limiting size, no further effect of population size on allele frequencies is expected, so isolated large populations will have closely similar allele frequencies if polymorphism is due largely to mutation and drift. The most common electrophoretic alleles are expected to be flanked by the next most common, with the rarer alleles increasingly distal. Neither strong selection nor mutation/drift interpretations of enzyme polymorphism are yet disproven, nor is any point between these extremes.

Polyallelic mutational equilibria.

A new deterministic formulation is derived of the equilibrium between mutation and natural selection, which takes into account(a) the possibility of many allelic mutation states, (b) selection coefficients of the order of magnitude of the mutation rate and (c) the possibility of further mutation of already mutant alleles. The frequencies of classes of alleles 0, 1, 2, n mutant steps removed from the type allele are shown to form a Poisson distribution, with a mean and variance of the mutation rate divided by the coefficient of selection against each incremental mutational step.--This formulation is interpreted in terms of the expected frequencies of electromorphs, defined as classes of alleles characterized by common electrophoretic mobilities of their protein products. Electromorph frequencies are predicted to form stable unimodal distributions of relatively few phenotypic classes. Common electromorph frequencies found throughout the ranges of species with large population sizes are interpreted as being a uniquely electrophoretic phenomenon; band patterns on starch and acrylamide gels are phenotypes, not genotypes. It is predicted that individual electromorphs are highly heterogenous with regard to amino acid sequence.

Immunological effects of an arginine side chain contaminating synthetically prepared peptides.

The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in order to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleavage process can be incomplete. We have found that animals injected with a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing peptide. This response is dependent on the characteristics of the MBP peptide involved. For two MBP peptides, the Mtr-containing peptide had increased binding to antibody over pure peptide. For two other peptides, only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident. These results provide further evidence that a small side chain on a single amino acid in a peptide can markedly alter the immunogenicity and antigenicity of that peptide for antibody reactivity. This evidence emphasizes the need for a critical awareness of each component of peptide synthesis and its potential to alter the immunoreactivity of the final product.

Contrast adaptation is spatial frequency specific in mouse primary visual cortex.

Contrast adaptation, generated by prolonged viewing of a high contrast spatial pattern, is known to reduce perceptual sensitivity to subsequently presented stimuli of similar spatial frequency (SF). Neural correlates of this pattern-specific contrast adaptation have been described in several classic studies in cat primary visual cortex (V1). These results have also recently been extended to mice, which is a genetically manipulable animal model. Here we attempt to parse the potential mechanisms contributing to this phenomenon by determining whether the SF specificity of contrast adaptation observed in mouse V1 neurons depends on the spike rate elicited by the adapting gratings. We found that adapting stimuli that drove a neuron more strongly generally produced more adaptation, implicating an intrinsic or fatigue-like process. Importantly, we also observed that slightly stronger contrast adaptation was produced when the adapting SF matched the test SF even when matched and nonmatched adapting gratings elicited similar spike rates indicating extrinsic or network processes contribute as well.

Distribution of two basement membrane proteoglycans through hair follicle development and the hair growth cycle in the rat.

The distribution of two distinct populations of basement membrane proteoglycans has been monitored through hair growth development in the rat embryo and subsequent hair growth cycle. An antiserum against a small heparan sulfate proteoglycan uniformly stained the dermal-epidermal junction of embryonic rats throughout the period of hair follicle formation. On the other hand, monoclonal antibodies recognizing a basement membrane-specific chondroitin sulfate proteoglycan only weakly stained 16-d embryo dermal-epidermal junction, but strong staining was associated with hair follicle buds as they developed. Through the hair growth cycle, it was found that the heparan sulfate proteoglycan persisted around the follicles, while the chondroitin sulfate proteoglycan decreased in amount through catagen until it was undetectable at the base and dermal papilla of the telogen follicle. As anagen commenced, expression of the chondroitin sulfate proteoglycan was again demonstrated. It therefore appears that a basement membrane-specific proteoglycan shows variation in its distribution in rat skin, expression correlating with morphogenetic activity in hair follicles. It is possible that this newly described basement membrane component is involved in the complex processes of dermal-epidermal interaction that lead to skin appendage formation and growth.

Clinical outcome of cardiac patients with negative thallium-201 SPECT and positive rubidium-82 PET myocardial perfusion imaging.

In a previous comparison of 202 consecutive patients who underwent myocardial perfusion imaging with both 201Tl SPECT and 82Rb PET, 27 patients were identified as having true-positive 82Rb images, but false-negative 201Tl images. The purpose of this report is to determine the effect of correct image interpretation of coronary artery disease on the final management of those patients and compare it to the previous management scheme wherein a negative image was usually accepted as the end point unless clinical symptoms dictated otherwise. A follow-up study of the clinical course and outcome of these studies showed that 63% (17/27) of the patients with a true-positive 82Rb PET image were recommended for revascularization procedures. It is doubtful that this majority of patients would have received either surgical or interventional management based on the false-negative 201Tl SPECT procedure alone.

Practical issues of experimental ROC analysis. Selection of controls.

Receiver operating characteristics (ROC) analysis has been used in many medical imaging applications during the past decade. With the recent expansion of the ROC methodology to multi-disease studies, several reports have begun to address both the theoretical and experimental design issues associated with such studies. While the appropriate selection, classification, and verification of actually positive cases is carefully addressed in the literature, similar considerations are rarely given to the selection of actually negative controls for these studies. In this paper, theoretical considerations and experimental data are provided to demonstrate the significance of this very issue.

Effect of two rating formats in multi-disease ROC study of chest images.

ROC methodology has been expanded in recent years to include multi-disease experiments. To accommodate these changes, different rating formats, general or disease specific, can be used. No experimental data are available concerning the possible effects of the rating format on the results of these studies. We performed a multi-observer, multi-disease study in which 196 chest images were rated using a format where each disease was evaluated individually and one in which the cases were evaluated without scoring a specific disease. The results indicate that for our data set, the overall assessment of accuracy was not significantly affected by the study format used. Thus, in spite of the difficulties in selecting appropriate controls and the necessity of reassessing sample size considerations, the disease-specific format appears to produce an assessment of accuracy equivalent to that produced by the general format. This equivalence permits the use of the disease-specific approach since it more closely simulates the readers' true environment and is more appropriate for comparing imaging systems that may have a relative accuracy that is disease specific.

Antenatal corticosteroids and newborn screening for congenital adrenal hyperplasia.

OBJECTIVE: To assess the effect of reported corticosteroid exposure on neonatal levels of 17-hydroxyprogesterone (17-OHP), the cortisol precursor used in newborn screening for congenital adrenal hyperplasia, in newborns weighing less than 2500 g at birth. DESIGN: A retrospective study of newborns weighing less than 2500 g at birth and exposed to corticosteroids as reported on their newborn screening card compared with newborns weighing less than 2500 g at birth and reported as not exposed to corticosteroids. METHODS: Birth weight, gestational age, age at screening, special care information, and name of screening hospital were obtained from newborn screening cards for 16 115 newborns screened in Michigan during the first 3 months of 2000. Levels of 17-OHP, measured by fluoroimmunoassay, were obtained from Michigan's Newborn Screening Program database. RESULTS: The mean 17-OHP level for the 69 low-birth-weight newborns in the corticosteroid-exposed group was 52 ng/mL, which was higher than that for the 771 low-birth-weight newborns in the unexposed group (35 ng/mL) (P<.001). Reported corticosteroid use did not decrease the number of expected borderline positive screening results for congenital adrenal hyperplasia (P>.05). Levels of 17-OHP varied by birth weight in corticosteroid-exposed and unexposed newborns. CONCLUSIONS: Corticosteroid exposure may not suppress screening 17-OHP levels. Therefore, newborn screening should not be delayed in premature newborns because of antenatal exposure to corticosteroids.

Analysis of angiotensin type 2 receptors in vasopressinergic neurons and pituitary in the rat.

Previous functional studies indicated that an angiotensin type 2 (AT2) receptor subtype may participate in the regulation of vasopressin release by angiotensin II (AngII). In the present study, AT2 receptor-directed antiserum immunohistochemically detected AT2 receptors within the hypothalamic paraventricular (PVN) and the supraoptic nuclei (SON) of the rat brain, more specifically, in identified vasopressinergic neurons. Considering the lack of AT2 binding in the PVN and the SON using receptor autoradiography, we tested the hypothesis that these AT2 receptors are transported to the posterior pituitary. Western blot analysis detected AT2 immunoreactivity in the posterior pituitary. However, no AT2 binding was detected in posterior pituitary membranes, and no AT2 binding was detected with quantitative receptor autoradiography in the neurohypophysis. Thus, if AT2 receptors are transported from the magnocellular vasopressin neurons to the posterior pituitary, their role in AngII regulation of vasopressin release at the neurohypophyseal terminals remains to be clarified.