868 research outputs found
Community-acquired pneumonia in critically ill very old patients: a growing problem
Very old (aged ≥80 years) adults constitute an increasing proportion of the global population. Currently, this subgroup of patients represents an important percentage of patients admitted to the intensive care unit. Community-acquired pneumonia (CAP) frequently affects very old adults. However, there are no specific recommendations for the management of critically ill very old CAP patients. Multiple morbidities, polypharmacy, immunosenescence and frailty contribute to an increased risk of pneumonia in this population. CAP in critically ill very old patients is associated with higher short- and long-term mortality; however, because of its uncommon presentation, diagnosis can be very difficult. Management of critically ill very old CAP patients should be guided by their baseline characteristics, clinical presentation and risk factors for multidrug-resistant pathogens. Hospitalisation in intermediate care may be a good option for critical ill very old CAP patients who do not require invasive procedures and for whom intensive care is questionable in terms of benefit
Respiratory viruses: their importance and lessons learned from COVID-19
Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses
Characteristics and Management of Community-Acquired Pneumonia in the Era of Global Aging
Community-acquired pneumonia (CAP) can occur at any time of life, but its incidence and risk of death are linked to increasing age. CAP in the elderly is a major health problem associated with high rates of readmission, morbidity, and mortality. Since the clinical presentation of pneumonia in the elderly may be atypical, clinicians should suspect pneumonia in older patients presenting symptoms such as falls and altered mental status, fatigue, lethargy, delirium, anorexia, in order to avoid the complications associated with delayed diagnosis and therapy. Streptococcus pneumoniae remains the most frequently reported pathogen in this population. However, particular attention should be paid to patients with risk factors for multidrug resistant pathogens, because a large proportion of elderly persons present multimorbidity. Vaccination is one of the most important preventive approaches for CAP in the elderly. In addition, lifestyle-tailored interventions for different modifiable risk factors will help to reduce the risk of pneumonia in elderly persons. Surveillance of etiological pathogens may improve vaccination policies in this population
A P System Based Model of an Ecosystem of Some Scavenger Birds
The Bearded Vulture (Gypaetus Barbatus) is an endangered species in Eu-
rope that feeds almost exclusively on bone remains provided by wild and domestic ungu-
lates. In [1], we presented a P system in order to study the evolution of these species in
the Pyrenees (NE Spain). Here, we present a new model that overcomes some limitations
of the previous work incorporating other scavenger species (predatory) and additional
prey species that provide food for the scavenger intraguild and interact with the Bearded
Vulture in the ecosystem. After the validation, the new model can be a useful tool for
the study of the evolution and management of the ecosystem. P systems provide a high
level computational modelling framework which integrates the structural and dynamical
aspects of ecosystems in a compressive and relevant way. The inherent randomness and
uncertainty in ecosystems is captured by using probabilistic strategies.Ministerio de Educación y Ciencia TIN2006-13425Junta de AndalucÃa P08–TIC-0420
P System Based Model of an Ecosystem of the Scavenger Birds
The Bearded Vulture (Gypaetus Barbatus) is an endangered species in Europe
that feeds almost exclusively on bone remains provided by wild and domestic ungulates.
In, we presented a P system in order to study the evolution of these species in
the Pyrenees (NE Spain). Here, we present a new model that overcomes some limitations
of the previous work incorporating other scavenger species (predatory) and additional
prey species that provide food for the scavenger intraguild and interact with the Bearded
Vulture in the ecosystem. After the validation, the new model can be a useful tool for
the study of the evolution and management of the ecosystem. P systems provide a high
level computational modelling framework which integrates the structural and dynamical
aspects of ecosystems in a compressive and relevant way. The inherent stochasticity and
uncertainty in ecosystems is captured by using probabilistic strategies.Ministerio de Educación y Ciencia TIN2006–13425Junta de AndalucÃa P08-TIC-0420
Identification, characterization and expression of novel Sex Hormone Binding Globulin alternative first exons in the human prostate
<p>Abstract</p> <p>Background</p> <p>The human Sex Hormone Binding Globulin (SHBG) gene, located at 17p13.1, comprises, at least, two different transcription units regulated by two different promoters. The first transcription unit begins with the exon 1 sequence and is responsible for the production of plasma SHBG by the hepatocytes, while the second begins with an alternative exon 1 sequence, which replaces the exon 1 present in liver transcripts. Alternative exon 1 transcription and translation has only been demonstrated in the testis of transgenic mice containing an 11-kb human SHBG transgene and in the human testis. Our goal has been to further characterize the 5' end of the SHBG gene and analyze the presence of the SHBG alternative transcripts in human prostate tissue and derived cell lines.</p> <p>Results</p> <p>Using a combination of <it>in silico </it>and <it>in vitro </it>studies, we have demonstrated that the SHBG gene, along with exon 1 and alternative exon 1 (renamed here exon 1A), contains four additional alternative first exons: the novel exons 1B, 1C, and 1E, and a previously identified exon 1N, which has been further characterized and renamed as exon 1D. We have shown that these four alternative first exons are all spliced to the same 3' splice site of SHBG exon 2, and that exon 1A and the novel exon 1B can be spliced to exon 1. We have also demonstrated the presence of SHBG transcripts beginning with exons 1B, 1C and 1D in prostate tissues and cell lines, as well as in several non-prostatic cell lines. Finally, the alignment of the SHBG mammalian sequences revealed that, while exons 1C, 1D and 1E are very well conserved phylogenetically through non-primate mammal species, exon 1B probably aroused in apes due to a single nucleotide change that generated a new 5' splice site in exon 1B.</p> <p>Conclusion</p> <p>The identification of multiple transcription start sites (TSS) upstream of the annotated first exon of human SHBG, and the detection of the alternative transcripts in human prostate, concur with the prediction of the ENCODE (ENCyclopedia of DNA Elements) project, and suggest that the regulation of SHBG is much more complex than previously reported.</p
A computational modeling for real ecosystems based on P systems
In this paper, a P systems based general framework for modeling ecosystems
dynamics is presented. Particularly, ecosystems are specified by means of multienvironment
P systems composed of a finite number of environments, each of them having an
extended P system with active membranes. The semantics is of a probabilistic type and it is
implemented by assigning each rule of the system a probabilistic constant which depends
on the environment and the run time. As a case study, two real ecosystems are described:
scavenger birds in the Catalan Pyrenees and the zebra mussel (Dreissena Polymorpha) in
Ribarroja reservoir (Spain).Ministerio de Ciencia e Innovación TIN2009–13192Junta de AndalucÃa P08–TIC-0420
Modeling Population Growth of Pyrenean Chamois (Rupicapra p. pyrenaica) by Using P-Systems
P systems provide a high level computational modeling framework which integrates the structural and dynamic aspects of ecosystems in a comprehensive and relevant way. In previous works, several ecosystems modeled by using P systems were presented. The good results obtained encourage us to study new ecosystems such as the one presented in this paper. Pyrenean Chamois (Rupicapra p. pyrenaica) is an ungulate species inhabiting the Catalan Pyrenees. In recent years, several diseases have caused a drastic decrease in the number of individuals. Since they provide significant economic contributions in the area and constitutes an important food resource for obligate and facultative scavengers, it is very interesting to provide a model in order to facilitate the management of their ecosystems
CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions
Enhancer regions and transcription start sites of estrogen-target regulated genes are connected by means of Estrogen Receptor long-range chromatin interactions. Yet, the complete molecular mechanisms controlling the transcriptional output of engaged enhancers and subsequent activation of coding genes remain elusive. Here, we report that CTCF binding to enhancer RNAs is enriched when breast cancer cells are stimulated with estrogen. CTCF binding to enhancer regions results in modulation of estrogen-induced gene transcription by preventing Estrogen Receptor chromatin binding and by hindering the formation of additional enhancer-promoter ER looping. Furthermore, the depletion of CTCF facilitates the expression of target genes associated with cell division and increases the rate of breast cancer cell proliferation. We have also uncovered a genomic network connecting loci enriched in cell cycle regulator genes to nuclear lamina that mediates the CTCF function. The nuclear lamina and chromatin interactions are regulated by estrogen-ER. We have observed that the chromatin loops formed when cells are treated with estrogen establish contacts with the nuclear lamina. Once there, the portion of CTCF associated with the nuclear lamina interacts with enhancer regions, limiting the formation of ER loops and the induction of genes present in the loop. Collectively, our results reveal an important, unanticipated interplay between CTCF and nuclear lamina to control the transcription of ER target genes, which has great implications in the rate of growth of breast cancer cells
Plasmodium falciparum Apicomplexan-Specific Glucosamine-6-Phosphate <i>N</i>-Acetyltransferase Is Key for Amino Sugar Metabolism and Asexual Blood Stage Development.
--- - i: - N - N - O - N - Plasmodium falciparum -
Cryptosporidium parvum - P. falciparum - N - N - P. falciparum -
C. parvum b: - IMPORTANCE content: - UDP- - "-acetylglucosamine
(UDP-GlcNAc), the main product of the hexosamine biosynthetic
pathway, is an important metabolite in protozoan parasites since
its sugar moiety is incorporated into
glycosylphosphatidylinositol (GPI) glycolipids and " - "- and "
- "-linked glycans. Apicomplexan parasites have a hexosamine
pathway comparable to other eukaryotic organisms, with the
exception of the glucosamine-phosphate " - "-acetyltransferase
(GNA1) enzymatic step that has an independent evolutionary
origin and significant differences from nonapicomplexan GNA1s.
By using conditional genetic engineering, we demonstrate the
requirement of GNA1 for the generation of a pool of UDP-GlcNAc
and for the development of intraerythrocytic asexual " - "
parasites. Furthermore, we present the 1.95\xE2\x80\x89\xC3\x85
resolution structure of the GNA1 ortholog from " - ", an
apicomplexan parasite which is a leading cause of diarrhea in
developing countries, as a surrogate for " - " GNA1. The
in-depth analysis of the crystal shows the presence of specific
residues relevant for GNA1 enzymatic activity that are further
investigated by the creation of site-specific mutants. The
experiments reveal distinct features in apicomplexan GNA1
enzymes that could be exploitable for the generation of
selective inhibitors against these parasites, by targeting the
hexosamine pathway. This work underscores the potential of
apicomplexan GNA1 as a drug target against malaria." - "
Apicomplexan parasites cause a major burden on global health and
economy. The absence of treatments, the emergence of resistances
against available therapies, and the parasite's ability to
manipulate host cells and evade immune systems highlight the
urgent need to characterize new drug targets to treat infections
caused by these parasites. We demonstrate that
glucosamine-6-phosphate " - -acetyltransferase (GNA1), required
for the biosynthesis of UDP- - "-acetylglucosamine (UDP-GlcNAc),
is essential for " - " asexual blood stage development and that
the disruption of the gene encoding this enzyme quickly causes
the death of the parasite within a life cycle. The
high-resolution crystal structure of the GNA1 ortholog from the
apicomplexan parasite " - ", used here as a surrogate,
highlights significant differences from human GNA1. These
divergences can be exploited for the design of specific
inhibitors against the malaria parasite.
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