Since 1973 the World Symposia on Pulmonary Hypertension (WSPH) proceedings have summarised the scientific advances and future needs in this field through the efforts of multiple task forces, each ...focusing on a different aspect of pulmonary hypertension (PH) 1. The 6th WSPH comprised 124 experts, divided into 13 task forces, that began their work in January 2017 and presented their consensus opinions to an audience of 1376 participant attendees between February 27 and March 1, 2018 in Nice, France. A newly created task force dedicated to patients' perspectives, including representatives of patients' associations worldwide, was added for the 6th WSPH.
State of the art summary on diagnosis, prognosis, therapy and future perspectives of pulmonary hypertension
http://ow.ly/8MHN30mGtqs
Viruses cannot replicate by themselves. Instead, they rely on the host for almost all their replicative functions. Similarly, many viruses are unable to cause damage without the host immune system. ...Because of this, two strategies can often ameliorate disease — antivirals, which block replication, and antiinflammatories, which can limit the damage induced by infection. In the lung, this latter strategy is exemplified by the treatment of
Pneumocystis jiroveci
, in which treatment with glucocorticoids reduces the severity of disease and the risk of death.
1,2
However, because blocking inflammatory pathways raises the possibility of diminishing the host response and increasing replication of . . .
In most bacteria, Clp protease is a conserved, non-essential serine protease that regulates the response to various stresses. Mycobacteria, including Mycobacterium tuberculosis (Mtb) and ...Mycobacterium smegmatis, unlike most well studied prokaryotes, encode two ClpP homologs, ClpP1 and ClpP2, in a single operon. Here we demonstrate that the two proteins form a mixed complex (ClpP1P2) in mycobacteria. Using two different approaches, promoter replacement, and a novel system of inducible protein degradation, leading to inducible expression of clpP1 and clpP2, we demonstrate that both genes are essential for growth and that a marked depletion of either one results in rapid bacterial death. ClpP1P2 protease appears important in degrading missense and prematurely terminated peptides, as partial depletion of ClpP2 reduced growth specifically in the presence of antibiotics that increase errors in translation. We further show that the ClpP1P2 protease is required for the degradation of proteins tagged with the SsrA motif, a tag co-translationally added to incomplete protein products. Using active site mutants of ClpP1 and ClpP2, we show that the activity of each subunit is required for proteolysis, for normal growth of Mtb in vitro and during infection of mice. These observations suggest that the Clp protease plays an unusual and essential role in Mtb and may serve as an ideal target for antimycobacterial therapy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Covid-19 epidemic continues to rage, especially in countries that have been unable or unwilling to institute strong public health measures. A return to normality has increasingly come to rely on ...the success of vaccines to prevent disease and, we hope, limit further spread of infection. However, this hope has been tempered by several unknowns. No existing vaccines have been shown to be effective against infection with any betacoronavirus, the family that includes SARS-CoV-2, which causes Covid-19. SARS, caused by another betacoronavirus, ended on its own before serious efforts at vaccine development were undertaken, and the rather small number of . . .
Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of ...conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.
Abstract Background Staphylococcus pseudintermedius has been recently identified as a novel species within the genus Staphylococcus , and is commonly associated with infections in dogs. Currently, ...there are few reports of human infections due to this bacterium. Objective To use a population-based approach to describe the characteristics of human S. pseudintermedius infections in a large Canadian healthcare region. Methods All adult cases aged ≥18 years identified at a large regional laboratory from April 1, 2013 to April 1, 2015 who had at least one positive culture for S. pseudintermedius were retrospectively reviewed. A combination of phenotypic methods, mass spectrometry (i.e., MALDI-TOF), and cpn 60 sequencing were used to identify S. pseudintermedius . Chart review was conducted, and cases were analysed descriptively. Results Twenty-seven isolates of S. pseudintermedius from 24 human cases were included for analysis. 58.3% were male with median age of 61 years (IQR 55–70.5). Most patients 22 (92.1%) had confirmed contact with dogs at time of infection. S. pseudintermedius was isolated in 18 cases (75.0%) of skin and soft tissue infections (SSTI), and 2 invasive cases (8.3%) including a prosthetic joint and bloodstream infection. The other 4 patients were considered to be colonized (skin – 3; lung – 1). Methicillin resistance was identified in 3 cases with 6 total isolates (22.2%); multi-drug resistance was also demonstrated commonly. Conclusion S. pseudintermedius is most commonly associated with SSTIs in humans. Transmission probably occurs from a pet dog. Species-level identification of S. pseudintermedius is important due to the high prevalence of antibiotic resistance, particularly to methicillin.
Fat Grafting for the Treatment of Scleroderma Strong, Amy L; Rubin, J Peter; Kozlow, Jeffrey H ...
Plastic and reconstructive surgery (1963),
2019-December, 2019-12-00, 20191201, Letnik:
144, Številka:
6
Journal Article
Recenzirano
BACKGROUND:Scleroderma is a chronic connective tissue disease that results in fibrosis of the skin and internal organs. Although internal organ involvement corresponds with poor prognosis, systemic ...agents are effective at improving the effects of scleroderma on internal organs. In contrast, skin manifestations are universally present in all patients diagnosed with scleroderma, yet no systemic agents have been shown to be successful. Fat grafting has been shown to improve skin quality and improve contour irregularities and may be helpful in the treatment of patients with scleroderma.
METHODS:The authors performed a thorough review of the pathophysiology of scleroderma and the current treatment options for scleroderma. The efficacy of fat grafting for the treatment of scleroderma and the mechanism by which fat grafting improves outcomes was also discussed.
RESULTS:Scleroderma is characterized by chronic inflammation and vascular compromise that leads to fibrosis of the skin and internal organs. Fat grafting has recently been the focus of significant basic science research. It has been shown to reduce inflammation, reduce fibrosis by limiting extracellular matrix proteins and increasing collagenase activity, and provide structural support through stem cell proliferation and differentiation. The adipocytes, adipose stem cells, endothelial cells, and vascular smooth muscle cells in the processed fat likely contribute to the effectiveness of this treatment.
CONCLUSIONS:Fat grafting in scleroderma patients likely improves skin manifestations by recreating fullness, correcting contour deformities, and improving skin quality. The injected fat provides a mixture of cells that influences the recipient site, resulting in improved outcomes.
We have generated a series of variable-strength, constitutive, bacterial promoters that act predictably in different sequence contexts, span two orders of magnitude in strength and contain convenient ...sites for cloning and the introduction of downstream open-reading frames. Importantly, their design insulates these promoters from the stimulatory or repressive effects of many 5'- or 3'-sequence elements. We show that different promoters from our library produce constant relative levels of two different proteins in multiple genetic contexts. This set of promoters should be a useful resource for the synthetic-biology community.
Background The Venous Thromboembolism Prevention Study (VTEPS) Network is a consortium of 5 tertiary referral centers established to examine venous thromboembolism (VTE) in plastic surgery patients. ...We report our midterm analyses of the study's control group to evaluate the incidence of VTE in patients who receive no chemoprophylaxis, and validate the Caprini Risk Assessment Model (RAM) in plastic surgery patients. Study Design Medical record review was performed at VTEPS centers for all eligible plastic surgery patients between March 2006 and June 2009. Inclusion criteria were Caprini score ≥3, surgery under general anesthesia, and postoperative hospital admission. Patients who received chemoprophylaxis were excluded. Dependent variables included symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) within the first 60 postoperative days and time to DVT or PE. Results We identified 1,126 historic control patients. The overall VTE incidence was 1.69%. Approximately 1 in 9 (11.3%) patients with Caprini score >8 had a VTE event. Patients with Caprini score >8 were significantly more likely to develop VTE when compared with patients with Caprini score of 3 to 4 (odds ratio OR 20.9, p < 0.001), 5 to 6 (OR 9.9, p < 0.001), or 7 to 8 (OR 4.6, p = 0.015). Among patients with Caprini score 7 to 8 or Caprini score >8, VTE risk was not limited to the immediate postoperative period (postoperative days 1-14). In these high-risk patients, more than 50% of VTE events were diagnosed in the late (days 15-60) postoperative period. Conclusions The Caprini RAM effectively risk-stratifies plastic and reconstructive surgery patients for VTE risk. Among patients with Caprini score >8, 11.3% have a postoperative VTE when chemoprophylaxis is not provided. In higher risk patients, there was no evidence that VTE risk is limited to the immediate postoperative period.
A striking neurochemical form of compartmentalization has been found in the striatum of humans and other species, dividing it into striosomes and matrix. The function of this organization has been ...unclear, but the anatomical connections of striosomes indicate their relation to emotion-related brain regions, including the medial prefrontal cortex. We capitalized on this fact by combining pathway-specific optogenetics and electrophysiology in behaving rats to search for selective functions of striosomes. We demonstrate that a medial prefronto-striosomal circuit is selectively active in and causally necessary for cost-benefit decision-making under approach-avoidance conflict conditions known to evoke anxiety in humans. We show that this circuit has unique dynamic properties likely reflecting striatal interneuron function. These findings demonstrate that cognitive and emotion-related functions are, like sensory-motor processing, subject to encoding within compartmentally organized representations in the forebrain and suggest that striosome-targeting corticostriatal circuits can underlie neural processing of decisions fundamental for survival.
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•A specific fronto-striatal decision circuit is activated by cost-benefit conflict•It primarily targets striatal striosomes, linked to limbic functions of striatum•Its optogenetic control selectively alters decisions under cost-benefit conflict•Its corticostriatal control is exerted through a striatal inhibitory microcircuit
Optogenetic manipulation and electrophysiology of a circuit connecting the prefrontal cortex to striosomes—compartmentalized structures of the striatum—reveals that it has a selective role in influencing decision-making for choices with cost-benefit tradeoffs.
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