353 research outputs found
Infrared spectrophotometric study of the Egyptian economic beach minerals as well as their alteration and weathering products
Senile Systemic Amyloidosis: Clinical Features at Presentation and Outcome
Background Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac‐isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors.
Methods and Results All patients with biopsy‐proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N‐terminal pro‐B‐type natriuretic peptide (NT pro‐BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro‐BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro‐BNP <1420 pmol/L.
Conclusions Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro‐BNP level can aid in distinguishing ATTRwt from AL amyloidosis
Minimally Invasive Video-Assisted Thyroidectomy and Parathyroidectomy with Intraoperative Recurrent Laryngeal Nerve Monitoring
Objective. Our goal is to study the feasibility of using intraoperative neuromonitoring (IONM) in minimally invasive video-assisted thyroidectomy and parathyroidectomy (MIVAT/P) with emphasis given to the identification of recurrent laryngeal nerve (RLN). Methods. Consecutive series of forty-seven patients with seventy-seven recurrent laryngeal nerves at risk undergoing both MIVAT/P and IONM were enrolled in this retrospective, nonrandomized analysis study. All operations were performed by the same surgeon within an academic institution setting. All patients underwent vocal cord evaluation postoperatively. Demographics and intraoperative and postoperative complications following surgery were collected. Results. Out of seventy-seven RLNs, there was one permanent unilateral RLN injury (1.29%) in a patient with advanced papillary thyroid cancer, managed by cord injection. There was another transient RLN paresis that resolved spontaneously (1.29%). There were no instances of equipment malfunction or interference. Conclusions. To our knowledge, this is the first reported MIVAT/P series from the United States of America with a standardized IONM technique. The technical feasibility of IONM seems acceptable and may serve as a meaningful adjunct to the visual identification of nerves. Neuromonitoring during MIVAT/P is effective in providing identification of laryngeal nerves and enables surgeons to feel more comfortable with MIVAT/P. Comparative series are needed for further evaluation
Sex-Chromosome Homomorphy in Palearctic Tree Frogs Results from Both Turnovers and X-Y Recombination
Contrasting with birds and mammals, poikilothermic vertebrates often have homomorphic sex chromosomes, possibly resulting from high rates of sex-chromosome turnovers and/or occasional X-Y recombination. Strong support for the latter mechanism was provided by four species of European tree frogs, which inherited from a common ancestor (∼5 Ma) the same pair of homomorphic sex chromosomes (linkage group 1, LG1), harboring the candidate sex-determining gene Dmrt1. Here, we test sex linkage of LG1 across six additional species of the Eurasian Hyla radiation with divergence times ranging from 6 to 40 Ma. LG1 turns out to be sex linked in six of nine resolved cases. Mapping the patterns of sex linkage to the Hyla phylogeny reveals several transitions in sex-determination systems within the last 10 My, including one switch in heterogamety. Phylogenetic trees of DNA sequences along LG1 are consistent with occasional X-Y recombination in all species where LG1 is sex linked. These patterns argue against one of the main potential causes for turnovers, namely the accumulation of deleterious mutations on nonrecombining chromosomes. Sibship analyses show that LG1 recombination is strongly reduced in males from most species investigated, including some in which it is autosomal. Intrinsically low male recombination might facilitate the evolution of male heterogamety, and the presence of important genes from the sex-determination cascade might predispose LG1 to become a sex chromosom
Metabolomics to unveil and understand phenotypic diversity between pathogen populations
Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance
PRC2 is dispensable for HOTAIR-mediated transcriptional repression
Long non-coding RNAs (lncRNAs) play diverse roles in physiological
and pathological processes. Several lncRNAs have been suggested
to modulate gene expression by guiding chromatin-modifying
complexes to specific sites in the genome. However, besides the
example of Xist, clear-cut evidence demonstrating this novel mode
of regulation remains sparse. Here, we focus on HOTAIR, a lncRNA
that is overexpressed in several tumor types and previously
proposed to play a key role in gene silencing through direct
recruitment of Polycomb Repressive Complex 2 (PRC2) to defined
genomic loci. Using genetic tools and a novel RNA-tethering
system, we investigated the interplay between HOTAIR and PRC2 in
gene silencing. Surprisingly, we observed that forced overexpression
of HOTAIR in breast cancer cells leads to subtle transcriptomic
changes that appear to be independent of PRC2. Mechanistically,
we found that artificial tethering of HOTAIR to chromatin causes
transcriptional repression, but that this effect does not require
PRC2. Instead, PRC2 recruitment appears to be a consequence of
gene silencing. We propose that PRC2 binding to RNA might serve
functions other than chromatin targeting
Antiphospholipid Antibodies Bind ATP: A putative Mechanism for the Pathogenesis of Neuronal Dysfunction
Antiphospholipid antibodies (aPL) generated in experimental animals
cross-react with ATP. We therefore examined the possibility that aPL IgG from
human subjects bind to ATP by affinity column and an enzyme linked
immunosorbent assay (ELISA). Sera with high levels of aPL IgG were collected
from 12 patients with the antiphospholipid syndrome (APS). IgG fractions from
10 of 12 APS patients contained aPL that could be affinity-bound to an ATP
column and completely eluted with NaCl 0.5 M. A significant (>50%) inhibition
of aPL IgG binding by ATP 5 mM was found in the majority. Similar inhibition
was obtained with ADP but not with AMP or cAMP. All the affinity purified
anti-ATP antibodies also bound β2-glycoprotein-I (β2-GPI, also known as
apolipoprotein H) suggesting that, similar to most pathogenic aPL, their binding
depends on this serum cofactor. We further investigated this possibility and found
that the binding of β2-GPI to the ATP column was similar to that of aPL IgG in
that most was reversed by NaCl 0.5 M. Furthermore, addition of β2-GPI to aPL
IgG significantly increased the amount of aPL binding to an ATP column. We
conclude that aPL IgG bind ATP, probably through β2-GPI. This binding could
interfere
with the normal extracellular function of ATP and similar neurotransmitters
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