1. The massive synchronized flowering and subsequent mortality of understorey bamboo species occur in infrequent and unpredictable intervals in temperate and subtropical forests around the world. ...Because of the sporadic occurrence of these flowering episodes and the long intervals between events, very little is known about their consequences on biogeochemical cycling in natural ecosystems. 2. In 2001, a synchronized flowering and dieback of the native bamboo, Chusquea culeou E.Desv., occurred, covering more than 200 000 ha in the north-west region of Patagonia, Argentina. We explored the impacts of this gregarious flowering event on litter decomposition and nitrogen turnover in an old-growth southern beech forest for 3 years after the flowering event. 3. Bamboo litter decomposed significantly slower than overstorey tree litter, and decomposition in flowered patches overall was significantly reduced compared to remnant live understorey patches. In addition, soil mineral nitrogen was reduced in flowered patches, and nitrogen transformations were altered, most notably in the third year after the flowering event. 4. This infrequent phenomenon of gregarious flowering could have consequences for carbon and nutrient cycling, as low-quality standing dead biomass is gradually incorporated into soil organic matter pools. This study demonstrates that large biotically mediated perturbations of understorey vegetation can impact biogeochemical cycles in temperate forest ecosystems by reducing carbon turnover and altering nitrogen availability and transformations, even in the absence of physical disturbance.
Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based ...therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found that MDS HSCs in two distinct differentiation states are maintained throughout the clinical course of the disease, and expand at progression, depending on recurrent activation of the anti-apoptotic regulator BCL-2 or nuclear factor-kappa B-mediated survival pathways. Pharmacologically inhibiting these pathways depleted MDS HSCs and reduced tumor burden in experimental systems. Further, patients with MDS who progressed after failure to frontline HMA therapy and whose HSCs upregulated BCL-2 achieved improved clinical responses to venetoclax-based therapy in the clinical setting. Overall, our study uncovers that HSC architectures in MDS are potential predictive biomarkers to guide second-line treatments after HMA failure. These findings warrant further investigation of HSC-specific survival pathways to identify new therapeutic targets of clinical potential in MDS.
Summary
Non‐alcoholic fatty liver disease is a new clinicopathological condition of emerging importance, now recognized as the most common cause of abnormal liver tests. It is characterized by a wide ...spectrum of liver damage: simple steatosis may progress to advanced fibrosis and to cryptogenic cirrhosis through steatohepatitis, and ultimately to hepatocellular carcinoma. Obesity is the most significant single risk factor for the development of fatty liver, both in children and in adults; obesity is also predictive of the presence of fibrosis, potentially progressing to advanced liver disease. From a pathogenic point of view, insulin resistance plays a central role in the accumulation of triglycerides within the hepatocytes and in the initiation of the inflammatory cascade. Chronic hepatocellular injury, necroinflammation, stellate cell activation, progressive fibrosis and ultimately, cirrhosis may be initiated by peroxidation of hepatic lipids and injury‐related cytokine release. In the last few years, several pilot studies have shown that treatment with insulin‐sensitizing agents, anti‐oxidants or cytoprotective drugs may be useful, but there is no evidence‐based support from randomized clinical trials. Modifications in lifestyle (e.g. diet and exercise) to reduce obesity remain the mainstay of prevention and treatment of a disease, which puts a large number of individuals at risk of advanced liver disease in the near future.
Context.
A significant fraction of all
γ
-ray sources detected by the Large Area Telescope aboard the
Fermi
satellite is still lacking a low-energy counterpart. In addition, there is still a large ...population of
γ
-ray sources with associated low-energy counterparts that lack firm classifications. In the last 10 years we have undertaken an optical spectroscopic campaign to address the problem of unassociated or unidentified
γ
-ray sources (UGSs), mainly devoted to observing blazars and blazar candidates because they are the largest population of
γ
-ray sources associated to date.
Aims.
Here we describe the overall impact of our optical spectroscopic campaign on sources associated in
Fermi
-LAT catalogs, coupled with objects found in the literature. In the literature search we kept track of efforts by different teams that presented optical spectra of counterparts or potential counterparts of
Fermi
-LAT catalog sources. Our summary includes an analysis of additional 30 newly collected optical spectra of counterparts or potential counterparts of
Fermi
-LAT sources of a previously unknown nature.
Methods.
New spectra were acquired at the
Blanco
4 m and OAN-SPM 2.1 m telescopes, and those available in the Sloan Digital Sky Survey (data release 15) archive.
Results.
All new sources with optical spectra analyzed here are classified as blazars. Thanks to our campaign, altogether we discovered and classified 394 targets with an additional 123 objects collected from a literature search. We began our optical spectroscopic campaign between the release of the second and third
Fermi
-LAT source catalogs (2FGL and 3FGL, respectively), classified about 25% of the sources that had uncertain nature and discovered a blazar-like potential counterpart for ∼10% of UGSs listed therein. In the 4FGL catalog, about 350
Fermi
-LAT sources have been classified to date thanks to our campaign.
Conclusions.
The most elusive class of blazars are found to be BL Lacs since the largest fraction of
Fermi
-LAT sources targeted in our observations showed a featureless optical spectrum. The same conclusion applied to the literature spectra. Finally, we confirm the high reliability of mid-IR color-based methods to select blazar-like candidate counterparts of unassociated or unidentified
γ
-ray sources.
To explore the available evidence on hyperosmolar therapies(HT) in mild and moderate traumatic brain injury(TBI) and to evaluate the effects on outcomes.
A scoping review was conducted according to ...the Joanna Briggs Institute methodology. Inclusion criteria: (a)randomized controlled trials(RCTs), prospective and retrospective cohort studies and case-control studies; (b)all-ages mild and moderate TBIs; (c)HT administration; (d)functional outcomes recorded; (e)comparator group.
From 4424 records, only 3 respected the inclusion criteria. In a retrospective cohort study of adult moderate TBIs, the Glasgow Coma Scale(GCS) remained the same at 48 hours in those treated with hypertonic saline(HTS) while it worsened in the non-treated. A trend toward increased pulmonary infections and length of stay was found. In an RCT of adult severe and moderate TBIs, moderate TBIs treated with HTS showed a trend toward better secondary outcomes than standard care alone, with similar odds of adverse effects. An RCT enrolling children with mild TBI found a significant improvement in concussive pain immediately after HTS administration and after 2-3 days. No adverse events occurred.
A gap in the literature about HTs' role in mild and moderate TBI was found. Some benefits may exist with limited side effects and further studies are desirable.
Purpose
To investigate the impact of diabetes in immigrants on the Italian healthcare system, as well as their compliance with standard protocols of control and treatment.
Methods
The prevalence of ...immigrants with diabetes living in the metropolitan area of Bologna (about 1 million inhabitants) in 2019 was investigated using a database containing all subjects in active follow-up for diabetes, based on antidiabetic drug use, disease-specific copayment exemption, ICD-9 codes, continuous care in diabetes units. Country of origin was derived from fiscal code.
Results
The overall prevalence of diabetes (n = 53,941; 51.8% males, median age 64) was 6.1% in both Italy-born and immigrant cohorts. Immigrant prevalence was 12.4%, moderately higher than that observed in the total population (12.2%). Diabetes risk was increased in the whole immigrant cohort (odds ratio (OR) 1.74; 95% Confidence Interval (CI) 1.69–1.79). Among cases with incident diabetes, the proportion of immigrants (median age, 49 vs. 65 in Italy-born individuals) increased progressively from 11.7% to 26.5% from 2011 to 2019 (males, 8.9–21.0%; females, 14.9–32.8%) in all age groups, particularly in young adults, but also in older subjects. Metabolic control was lower in immigrants, as was adherence to shared diagnostic and therapeutic protocols, without systematic differences in antidiabetic drug use, but much lower use of drugs for comorbid conditions.
Conclusions
The population with diabetes in the metropolitan area of Bologna is rapidly changing. Quality improvement initiatives are needed to reduce the burden for the universalistic Italian health care system generated by the rapidly-growing high-risk immigrant population.
Phosphatidylcholine (PC), a common phospholipid of the eukaryotic cell membrane, is present in the cell envelope of the intracellular pathogen Brucella abortus, the etiological agent of bovine ...brucellosis. In this pathogen, the biosynthesis of PC proceeds mainly through the phosphatidylcholine synthase pathway; hence, it relies on the presence of choline in the milieu. These observations imply that B. abortus encodes an as-yet-unknown choline uptake system. Taking advantage of the requirement of choline uptake for PC synthesis, we devised a method that allowed us to identify a homologue of ChoX, the high-affinity periplasmic binding protein of the ABC transporter ChoXWV. Disruption of the choX gene completely abrogated PC synthesis at low choline concentrations in the medium, thus indicating that it is a high-affinity transporter needed for PC synthesis via the PC synthase (PCS) pathway. However, the synthesis of PC was restored when the mutant was incubated in media with higher choline concentrations, suggesting the presence of an alternative low-affinity choline uptake activity. By means of a fluorescence-based equilibrium-binding assay and using the kinetics of radiolabeled choline uptake, we show that ChoX binds choline with an extremely high affinity, and we also demonstrate that its activity is inhibited by increasing choline concentrations. Cell infection assays indicate that ChoX activity is required during the first phase of B. abortus intracellular traffic, suggesting that choline concentrations in the early and intermediate Brucella-containing vacuoles are limited. Altogether, these results suggest that choline transport and PC synthesis are strictly regulated in B. abortus.
Choloylglycine hydrolase (CGH, E.C. 3.5.1.24) is a conjugated bile salt hydrolase that catalyses the hydrolysis of the amide bond in conjugated bile acids. Bile salt hydrolases are expressed by ...gastrointestinal bacteria, and they presumably decrease the toxicity of host's conjugated bile salts. Brucella species are the causative agents of brucellosis, a disease affecting livestock and humans. CGH confers Brucella the ability to deconjugate and resist the antimicrobial action of bile salts, contributing to the establishment of a successful infection through the oral route in mice. Additionally, cgh-deletion mutant was also attenuated in intraperitoneally inoculated mice, which suggests that CGH may play a role during systemic infection other than hydrolyzing conjugated bile acids. To understand the role CGH plays in B. abortus virulence, we infected phagocytic and epithelial cells with a cgh-deletion mutant (Δcgh) and found that it is defective in the internalization process. This defect along with the increased resistance of Δcgh to the antimicrobial action of polymyxin B, prompted an analysis of the cell envelope of this mutant. Two-dimensional electrophoretic profiles of Δcgh cell envelope-associated proteins showed an altered expression of Omp2b and different members of the Omp25/31 family. These results were confirmed by Western blot analysis with monoclonal antibodies. Altogether, the results indicate that Brucella CGH not only participates in deconjugation of bile salts but also affects overall membrane composition and host cell internalization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To explore the experience of using audience response systems (ARS) in postgraduate physiotherapy training.
Design
Qualitative interview study following the ‘reflexive thematic analysis’ by ...Braun and Clarke.
Setting
Higher education university.
Participants
Ten Italian students (60% men, N=6; 40% women, N=4) agreed to partake in the interviews.
Results
We generated four themes. Specifically, the ARS were perceived: (1) as a ‘Shared Compass’ (theme 1) between the student and the lecturers to monitor and modify the ongoing students’ learning journey; (2) useful to ‘Come Out of Your Shell’ (theme 2) as they help students to overcome shyness and build a team with peers; (3) as ‘A Square Peg in a Round Hole’ (theme 3) as they should not be used in situations that do not suit them; (4) as ‘Not Everyone’s Cup of Tea’ (theme 4) as mixed opinions among ARS’ utilities were found under some circumstances (eg, memorisation process and clinical reasoning).
Conclusion
Physiotherapy lecturers must use ARS critically, respecting when (eg, not at the end of the lesson) and how to propose them, keeping in mind that some skills (eg, practical ones) might not benefit from their use. Moreover, they need to consider that the ARS are not a tool for everyone, so ARS must be integrated into a multimodal teaching paradigm.
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