“Surgical” Abdomen in a Patient with Chronic Lymphocytic Leukemia: A Case of Acquired Angioedema

# The Author(s) 2011. This article is published with open access at Springerlink.com Introduction Acquired angioedema (AAE), an acquired deficiency of C1esterase inhibitor, is a medically treatable condition which can cause severe abdominal pain mimicking an acute surgical abdomen. This disorder is strongly associated with chronic lymphocytic leukemia (CLL) and other indolent lymphoplasmacytic disorders. Discussion We describe a patient with known CLL who developed incapacitating, recurrent severe abdominal pains, culminating in partial bowel resection. Signs, symptoms, laboratory and pathologic findings demonstrated AAE

Are parents identifying positive aspects to parenting their child with an intellectual disability or are they just coping? A qualitative exploration

Although acknowledging the stress of raising their child with intellectual disabilities, parents also report that their child has brought about many positive changes in themselves and family. This study reports what parents perceive to be a positive aspect of parenting their child, as currently what constitutes a ‘positive’ is unclear. Seven key themes were identified; an increased sense of personal strength and confidence, changed priorities, greater appreciation of life, pleasure in the child’s accomplishments, increased faith/spirituality, more meaningful relationships and the positive effect that the child has on the wider community. Interpretive examination of the themes reveals that the positive aspects identified consist mostly of meaning-focused coping strategies. These enable parents to adapt successfully to the stressful experiences of raising their child and therefore could be amenable to meaning-focused therapeutic interventions for parents with newly diagnosed children or for those unable to identify any positive aspects of parenting their child

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa

<p>Abstract</p> <p>Background</p> <p>Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection.</p> <p>Presentation of the hypothesis</p> <p>Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity.</p> <p>Testing the Hypothesis</p> <p>The hypothesis is testable by exposing different virus genotypes to ultra-violet radiation and quantifying virus survival by plaque forming units or quantitative mRNA RT-PCR.</p> <p>Implications of the hypothesis</p> <p>The ancestral varicella-zoster virus, most probably a tropical genotype, co-migrated with man as he left Africa approximately 200,000 years ago. For this virus to have lost the selective advantage of resistance to ultra-violet radiation, the hypothesis would predict that the temperate, ultra-violet sensitive virus should have acquired another selective advantage as an evolutionary trade-off. One obvious advantage could be an increased reactivation rate as zoster to set up more rounds of chickenpox transmission. If this were so, the mechanism responsible for resistance to ultra-violet radiation might also be involved in reactivation and latency. This could then provide the first insight into a genetic correlate of the survival strategy of this virus.</p

Does Alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women

BACKGROUND: Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s) and incorporate prior knowledge of alendronate efficacy in women in the analysis. METHODS: We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions) for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004), and Embase (1996–2004). We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men), which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women. RESULTS: The odds ratios of incident fractures in men (with 95% credibility intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23, 0.83) and non-vertebral fractures, 0.60 (0.29, 1.44). CONCLUSION: In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect

Environmental variables, habitat discontinuity and life history shaping the genetic structure of Pomatoschistus marmoratus

Coastal lagoons are semi-isolated ecosystems exposed to wide fluctuations of environmental conditions and showing habitat fragmentation. These features may play an important role in separating species into different populations, even at small spatial scales. In this study, we evaluate the concordance between mitochondrial (previous published data) and nuclear data analyzing the genetic variability of Pomatoschistus marmoratus in five localities, inside and outside the Mar Menor coastal lagoon (SE Spain) using eight microsatellites. High genetic diversity and similar levels of allele richness were observed across all loci and localities, although significant genic and genotypic differentiation was found between populations inside and outside the lagoon. In contrast to the FST values obtained from previous mitochondrial DNA analyses (control region), the microsatellite data exhibited significant differentiation among samples inside the Mar Menor and between lagoonal and marine samples. This pattern was corroborated using Cavalli-Sforza genetic distances. The habitat fragmentation inside the coastal lagoon and among lagoon and marine localities could be acting as a barrier to gene flow and contributing to the observed genetic structure. Our results from generalized additive models point a significant link between extreme lagoonal environmental conditions (mainly maximum salinity) and P. marmoratus genetic composition. Thereby, these environmental features could be also acting on genetic structure of coastal lagoon populations of P. marmoratus favoring their genetic divergence. The mating strategy of P. marmoratus could be also influencing our results obtained from mitochondrial and nuclear DNA. Therefore, a special consideration must be done in the selection of the DNA markers depending on the reproductive strategy of the species

A distal region of the human TGM1 promoter is required for expression in transgenic mice and cultured keratinocytes

BACKGROUND: TGM1(transglutaminase 1) is an enzyme that crosslinks the cornified envelope of mature keratinocytes. Appropriate expression of the TGM1 gene is crucial for proper keratinocyte function as inactivating mutations lead to the debilitating skin disease, lamellar ichthyosis. TGM1 is also expressed in squamous metaplasia, a consequence in some epithelia of vitamin A deficiency or toxic insult that can lead to neoplasia. An understanding of the regulation of this gene in normal and abnormal differentiation states may contribute to better disease diagnosis and treatment. METHODS: In vivo requirements for expression of the TGM1 gene were studied by fusing various lengths of promoter DNA to a reporter and injecting the DNA into mouse embryos to generate transgenic animals. Expression of the reporter was ascertained by Western blotting and immunohistochemistry. Further delineation of a transcriptionally important distal region was determined by transfections of progressively shortened or mutated promoter DNA into cultured keratinocytes. RESULTS: In vivo analysis of a reporter transgene driven by the TGM1 promoter revealed that 1.6 kilobases, but not 1.1 kilobases, of DNA was sufficient to confer tissue-specific and cell layer-specific expression. This same region was responsible for reporter expression in tissues undergoing squamous metaplasia as a response to vitamin A deprivation. Mutation of a distal promoter AP1 site or proximal promoter CRE site, both identified as important transcriptional elements in transfection assays, did not prevent appropriate expression. Further searching for transcriptional elements using electrophoretic mobility shift (EMSA) and transfection assays in cultured keratinocytes identified two Sp1 elements in a transcriptionally active region between -1.6 and -1.4 kilobases. While mutation of either Sp1 site or the AP1 site singly had only a small effect, mutation of all three sites eliminated nearly all the transcriptional activity. CONCLUSIONS: A distal region of the TGM1 gene promoter, containing AP1 and Sp1 binding sites, is evolutionarily conserved and responsible for high level expression in transgenic mice and in transfected keratinocyte cultures

Genome-wide association study of male sexual orientation

Family and twin studies suggest that genes play a role in male sexual orientation. We conducted a genome-wide association study (GWAS) of male sexual orientation on a primarily European ancestry sample of 1,077 homosexual men and 1,231 heterosexual men using Affymetrix single nucleotide polymorphism (SNP) arrays. We identified several SNPs with p < 10 -5 , including regions of multiple supporting SNPs on chromosomes 13 (minimum p = 7.5 × 10 -7 ) and 14 (p = 4.7 × 10 -7 ). The genes nearest to these peaks have functions plausibly relevant to the development of sexual orientation. On chromosome 13, SLITRK6 is a neurodevelopmental gene mostly expressed in the diencephalon, which contains a region previously reported as differing in size in men by sexual orientation. On chromosome 14, TSHR genetic variants in intron 1 could conceivably help explain past findings relating familial atypical thyroid function and male homosexuality. Furthermore, skewed X chromosome inactivation has been found in the thyroid condition, Graves' disease, as well as in mothers of homosexual men. On pericentromeric chromosome 8 within our previously reported linkage peak, we found support (p = 4.1 × 10 -3 ) for a SNP association previously reported (rs77013977, p = 7.1 × 10 -8 ), with the combined analysis yielding p = 6.7 × 10 -9 , i.e., a genome-wide significant association

Mining protein loops using a structural alphabet and statistical exceptionality

<p>Abstract</p> <p>Background</p> <p>Protein loops encompass 50% of protein residues in available three-dimensional structures. These regions are often involved in protein functions, e.g. binding site, catalytic pocket... However, the description of protein loops with conventional tools is an uneasy task. Regular secondary structures, helices and strands, have been widely studied whereas loops, because they are highly variable in terms of sequence and structure, are difficult to analyze. Due to data sparsity, long loops have rarely been systematically studied.</p> <p>Results</p> <p>We developed a simple and accurate method that allows the description and analysis of the structures of short and long loops using structural motifs without restriction on loop length. This method is based on the structural alphabet HMM-SA. HMM-SA allows the simplification of a three-dimensional protein structure into a one-dimensional string of states, where each state is a four-residue prototype fragment, called structural letter. The difficult task of the structural grouping of huge data sets is thus easily accomplished by handling structural letter strings as in conventional protein sequence analysis. We systematically extracted all seven-residue fragments in a bank of 93000 protein loops and grouped them according to the structural-letter sequence, named structural word. This approach permits a systematic analysis of loops of all sizes since we consider the structural motifs of seven residues rather than complete loops. We focused the analysis on highly recurrent words of loops (observed more than 30 times). Our study reveals that 73% of loop-lengths are covered by only 3310 highly recurrent structural words out of 28274 observed words). These structural words have low structural variability (mean RMSd of 0.85 Å). As expected, half of these motifs display a flanking-region preference but interestingly, two thirds are shared by short (less than 12 residues) and long loops. Moreover, half of recurrent motifs exhibit a significant level of amino-acid conservation with at least four significant positions and 87% of long loops contain at least one such word. We complement our analysis with the detection of statistically over-represented patterns of structural letters as in conventional DNA sequence analysis. About 30% (930) of structural words are over-represented, and cover about 40% of loop lengths. Interestingly, these words exhibit lower structural variability and higher sequential specificity, suggesting structural or functional constraints.</p> <p>Conclusions</p> <p>We developed a method to systematically decompose and study protein loops using recurrent structural motifs. This method is based on the structural alphabet HMM-SA and not on structural alignment and geometrical parameters. We extracted meaningful structural motifs that are found in both short and long loops. To our knowledge, it is the first time that pattern mining helps to increase the signal-to-noise ratio in protein loops. This finding helps to better describe protein loops and might permit to decrease the complexity of long-loop analysis. Detailed results are available at <url>http://www.mti.univ-paris-diderot.fr/publication/supplementary/2009/ACCLoop/</url>.</p

Structural hierarchies define toughness and defect-tolerance despite simple and mechanically inferior brittle building blocks

Mineralized biological materials such as bone, sea sponges or diatoms provide load-bearing and armor functions and universally feature structural hierarchies from nano to macro. Here we report a systematic investigation of the effect of hierarchical structures on toughness and defect-tolerance based on a single and mechanically inferior brittle base material, silica, using a bottom-up approach rooted in atomistic modeling. Our analysis reveals drastic changes in the material crack-propagation resistance (R-curve) solely due to the introduction of hierarchical structures that also result in a vastly increased toughness and defect-tolerance, enabling stable crack propagation over an extensive range of crack sizes. Over a range of up to four hierarchy levels, we find an exponential increase in the defect-tolerance approaching hundred micrometers without introducing additional mechanisms or materials. This presents a significant departure from the defect-tolerance of the base material, silica, which is brittle and highly sensitive even to extremely small nanometer-scale defects