Abstract
Infections by multidrug-resistant
Enterobacteriaceae
(MRE) are life-threatening to patients. The intestinal microbiome protects against MRE colonization, but antibiotics cause collateral ...damage to commensals and open the way to colonization and subsequent infection. Despite the significance of this problem, the specific commensals and mechanisms that restrict MRE colonization remain largely unknown. Here, by performing a multi-omic prospective study of hospitalized patients combined with mice experiments, we find that
Lactobacillus
is key, though not sufficient, to restrict MRE gut colonization.
Lactobacillus rhamnosus
and
murinus
increase the levels of Clostridiales bacteria, which induces a hostile environment for MRE growth through increased butyrate levels and reduced nutrient sources. This mechanism of colonization resistance, an interaction between
Lactobacillus
spp. and Clostridiales involving cooperation between microbiota members, is conserved in mice and patients. These results stress the importance of exploiting microbiome interactions for developing effective probiotics that prevent infections in hospitalized patients.
The advent of all-trans-retinoic acid (ATRA) and its combination with anthracycline-containing chemotherapy have contributed in the past 2 decades to optimize the antileukemic efficacy in acute ...promyelocytic leukemia (APL), leading to complete remission rates greater than 90%, virtual absence of resistance, and cure rates of nearly 80%. Recently reported studies from large cooperative trials have also shown that more rational delivery of treatment and improved outcomes may derive from the use of risk-adapted protocols. In particular, patients at higher risk of relapse (ie, those presenting with WBC > 10 × 10(9)/L) seem to benefit from treatments that include cytarabine in the ATRA-plus-chemotherapy scheme, whereas patients with standard-risk disease can be successfully managed with less-intensive regimens that contain ATRA and anthracycline-based chemotherapy. After the outstanding results with arsenic trioxide (ATO) in the treatment of APL relapse, several experimental trials have been designed to explore the role of ATO in front-line therapy with the aim not only of minimizing the use of chemotherapy but also to reinforce standard ATRA-plus-chemotherapy regimens and additionally improve therapeutic efficacy. In this review article, we discuss most recent advances in the treatment of patients with newly diagnosed and relapsed APL.
Differentiation syndrome (DS), formerly known as retinoic acid syndrome, is a relatively common and potentially severe complication seen in patients with acute promyelocytic leukemia treated with ...all-trans retinoic acid and/or arsenic trioxide. The full-blown syndrome consists of unexplained fever, weight gain, dyspnea with pulmonary infiltrates, pleuropericardial effusion, hypotension, and renal failure. Most measures currently used for management of DS have very little evidence-based support, and therefore, many remain controversial. Despite the lack of evidence supporting DS prophylaxis, several groups have adopted a preventive strategy with corticosteroids, especially for patients with leukocyte levels higher than from 5 to 10 × 109/L. DS diagnosis should be suspected in the presence of any of the above-mentioned signs and symptoms, and preemptive treatment with dexamethasone should be started immediately. Other supportive measures can also be crucial for the correct management of DS, especially in those patients with life-threatening complications. Temporary discontinuation of all-trans retinoic acid or arsenic trioxide is indicated only for patients in very poor clinical condition or with severe renal or pulmonary dysfunction, sometimes requiring admission to the intensive care unit. Recognition of specific biomarkers and a better understanding of DS pathogenesis can be helpful for the development of specific therapies to counteract DS in a timely manner.
The structural and electronic properties of the alizarin dye supported on TiO2 nanoclusters have been examined by means of time-dependent density-functional (TD-DFT) calculations performed in the ...time-domain framework. The calculated electronic absorption spectrum of free alizarin shows a first band centered at 2.67 eV that upon adsorption features a red shift by 0.31 eV, in agreement with both experimental and previous theoretical work. This red shift arises from a relative stabilization of the dye LUMO when adsorbed. To analyze the dependence of the electronic properties of the dye-support couple on the size of metal-oxide nanoparticles, different models of (TiO2) n nanoclusters have been used (with n = 1, 2, 3, 6, 9, 15, and 38). As a conclusion, the minimal model is good enough to theoretically reproduce the main feature in the spectrum (i.e., the energy shift of the main band upon binding to TiO2). However, it fails in creating intermediate states which could play a significant role under real experimental conditions (dynamics of the electronic transfer). Indeed, as the size of the nanocluster grows, the dye LUMO moves from the edge to well inside the conduction band (Ti 3d band). On the other hand, to assess the consistency of the time-domain approach in the case of such systems, conventional (frequency-domain) TD-DFT calculations have been carried out. It is found that, as far as the functional and basis set are equivalent, both approaches lead to similar results. While for small systems the standard TD-DFT is better suited, for medium to large sized systems, the real-time TD-DFT becomes competitive and more efficient.
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of ...arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion–based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all-trans retinoic acid– and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.
Since the introduction of all-trans retinoic acid and, more recently, arsenic trioxide into the therapy of acute promyelocytic leukemia (APL), significant improvements in patient outcomes have been ...achieved, and this disease has become the most curable subtype of acute myeloid leukemia. However, while primary leukemia resistance has virtually disappeared, a sizable fraction of APL patients still die before or during induction therapy. Hemorrhagic death still remains the major problem during this early phase of treatment and, to a lesser extent, deaths due to infection, differentiation syndrome and other causes. Patients with APL typically present with a range of laboratory abnormalities consistent with the diagnosis of disseminated intravascular coagulation and hyperfibrinolysis. This APL-associated coagulopathy, as a result of a dysregulation of the hemostatic system due to the imbalance between procoagulant, anticoagulant and profibrinolytic mechanisms, may show a variety of clinical manifestations, ranging from minimal bleeding or localized thrombosis to lethal or life-threatening hemorrhages or thrombotic events that sometimes occur concomitantly. Hemorrhagic events are the most common cause of death associated with APL coagulopathy, but thrombosis, a less recognized and probably underestimated life-threatening manifestation of the thrombo-hemorrhagic syndrome, is also a non-negligible cause of morbidity and mortality in patients with APL. In this article, we aim to discuss recent advances in the knowledge of pathogenesis, predictors of thrombo-hemorrhagic events, management of coagulopathy associated with APL and the controversial issues that still persist.
Skipped diynones, efficiently prepared from biomass-derived ethyl lactate, undergo a tandem hydration–oxacyclization reaction under gold(I) catalysis. Reaction conditions have been developed for a ...switchable process that allows selective access to 4-pyrones or 3(2H)-furanones from the same starting diynones. Further application of this methodology in the total synthesis of polyporapyranone B was demonstrated.
Accessible Summary
What is known on the subject?
Humanizing the world of health is a complex process that includes all the dimensions of the person. When a person has from a mental illness, the ...humanization of care becomes more important, as the disorder itself prevents the person to participate in their health process, even when showing self‐harm or aggressive behaviours.
These situations jointly with other factors related with professionals (insufficient ratio, inadequate treatment or lack of training) may cause the patient admitted to the acute psychiatric hospitalization unit to require the use of restrictive measures (involuntary admissions, mechanical restraints or forced administration of medication).
What the paper adds to existing knowledge?
We identify the relevance of the perception the patient and family have regarding the care received, as well as the relevance of factors related to the professionals, among which the attitude, the staff ratio, the nursing time of direct dedication, and the therapeutic environment and safety of the patient and the professionals. All patients must be treated with dignity, respect, regardless of the aggressive manifestations caused by their pathology.
What are the implications for practice?
A greater understanding of the care offered to admitted people affected by a mental disorder, their families and professionals who care for them in acute mental health units, giving greater importance to “caring” and not exclusively to “curing.”
Introduction
Humanization in Mental Health refers to give the same relevance to the clinical needs and to the social, emotional and psychological needs.
Aim
To identify the published knowledge on current care models related to the humanization of care in acute psychiatric units.
Method
Scoping review based on the methodological model of Arksey and O'Malley, and PRISMA methodology. Database searches (Pubmed, Cinahl, Virtual Library, Cuiden, Academic Google and PsycInfo) with the terms: “Humanization,” “Hospitals Psychiatric,” “Emergency Psychiatric,” “Psychiatric Service” and “Psychiatric intensive care units.”
Results
Twenty‐two articles met the inclusion criteria. Four thematic units were identified: aspects related to (i) patient perceptions; (ii) Government policies and hospitality organizational culture; (iii) external factors such as the environment, family or associations; and (iv) safety and security.
Discussion
Only one of the articles mentions the concept analysed, although all of them contribute with key aspects of healthcare humanization, such as the empowerment of the patient, the care model, the staff ratio, the therapeutic relationship, the nursing time of direct dedication to the patient, the therapeutic environment, safety and patient and staff perception of feeling safe.
Implications for Practice
The present study can help to improve the care offered in acute mental health units.
The bicyclic terpenoid fenchone (C10H16O, 1,3,3-trimethylbicyclo2.2.1heptan-2-one) has been investigated by chirped pulse Fourier transform microwave spectroscopy in the 2-8 GHz frequency region. The ...parent species and all heavy atom isotopologues have been observed in their natural abundance. The experimental rotational constants of all isotopic species observed have been determined and used to obtain the substitution (rs) and effective (r0) structures of fenchone. Calculations at the B3LYP, M06-2X, and MP2 levels of theory with different basis sets were carried out to check their performance against experimental results. The structure of fenchone has been compared with those of norbornane (bicyclo2.2.1heptane) and the norbornane derivatives camphor (1,7,7-trimethylbicyclo2.2.1heptan-2-one) and camphene (3,3-dimethyl-2-methylenebicyclo2.2.1heptane), both with substituents at C2. The structure of fenchone is remarkably similar to those of camphor and camphene. Comparison with camphor allows identification of changes in ∠CCC angles due to the different position of the methyl groups. All norbornane derivatives display similar structural changes with respect to norbornane. These changes mainly affect the bond lengths and angles of the six-membered rings, indicating that the substituent at C2 drives structural adjustments to minimise ring strain after its introduction.
Diagnosis and management of immune thrombocytopenic purpura (ITP) remain largely dependent on clinical expertise and observations more than on evidence derived from clinical trials of high scientific ...quality. One major obstacle to the implementation of such studies and in producing reliable meta-analyses of existing data is a lack of consensus on standardized critical definitions, outcome criteria, and terminology. Moreover, the demand for comparative clinical trials has dramatically increased since the introduction of new classes of therapeutic agents, such as thrombopoietin receptor agonists, and innovative treatment modalities, such as anti-CD 20 antibodies. To overcome the present heterogeneity, an International Working Group of recognized expert clinicians convened a 2-day structured meeting (the Vicenza Consensus Conference) to define standard terminology and definitions for primary ITP and its different phases and criteria for the grading of severity, and clinically meaningful outcomes and response. These consensus criteria and definitions could be used by investigational clinical trials or cohort studies. Adoption of these recommendations would serve to improve communication among investigators, to enhance comparability among clinical trials, to facilitate meta-analyses and development of therapeutic guidelines, and to provide a standardized framework for regulatory agencies.
PDF
