The ferric form of reindeer hemoglobin (Rangifer tarandus tarandus) has been crystallized in an orthorhombic crystalline form from polyethylene glycol solutions, at pH 8.2. The crystals belong to the ...orthorhombic space group P2(1)2(1)2(1), with unit cell edges a = 84.2 A, b = 59.9 A, c = 119.5 A; one hemoglobin tetramer is contained in the asymmetric unit. The crystals diffract X-rays to a limit spacing of 3.0 A. Inspection of amino acid sequences in the N-terminal region of beta-chains, and analysis of hemoglobin three-dimensional models, allows one to rationalize, on a molecular basis, the reduced O2 affinity and the decreased effect of organic phosphates observed in ruminant hemoglobins. By analogy, the analysis is extended to birds and reptiles, whose hemoglobin beta-chains display, as in ruminants, the deletion of the N-terminal residue and a methionine at the NA2 position.
Cytoplasmic monomeric hemoglobin I from the bacteria-harboring gill of the bivalve mollusc Lucina pectinata has been crystallized in a form suitable for atomic resolution X-ray structural ...investigations. The crystals have been grown at pH 4.8, in 0.05 M-acetate buffer, using 2.6 M-ammonium sulfate as precipitating agent. The crystals belong to the monoclinic space group P2(1), with unit cell constants a = 50.0 A, b = 38.6 A, c = 42.1 A, beta = 107.1 degrees, and contain one molecule (14,000 Mr) in the asymmetric unit. By means of single crystal microspectrophotometry it has been shown that the crystals contain the ferric form of L. pectinata "sulfide reactive" hemoglobin I. On the other hand, by careful control of the buffering medium composition, it has been possible to obtain stable crystals of the deoxy, oxy and sulfide forms of the protein.
A monoclonal IgG antibody directed against gp 41 from the human immunodeficiency virus (HIV-1) has been crystallized in both intact and Fab forms. Crystals of the intact antibody grow as ...tetragonal-like prisms too small for conventional X-ray analysis. However, the Fab portion of the antibody produces suitable plate-like crystals which belong to the space group P2(1)2(1)2(1) with unit cell constants of a = 66.5 A, b = 74.3 A and c = 105.3 A. There is one molecule of Fab in the asymmetric unit. The Fab crystals show diffraction to d-spacings less than 3.0 A.
A new gelatinous matrix is reported, having intermediate properties between those of polyacrylamide and agarose gels. The matrix has the unique property of being amphiphilic, i.e. of swelling in both ...plain water and polar organic solvents, and seems particularly well suited for electrophoresis of DNA. The compatibility with organic solvents includes 50% dimethyl sulphoxide, 50% tetramethyl urea, 50% acetonitrile and 50% tetrahydrofuran, the latter having a dielectric constant of 20. The matrix is hypothesized to consist of brush-like pillars, having a hydrophobic core and a hydrophilic coating. The latter is formed by short chains protruding in the surrounding liquid and able to coordinate large amounts of water.
Alzheimer's disease (AD) and dementia are chronic diseases with progressive deterioration of cognition, function, and behavior leading to severe disability and death. The prevalence of AD and ...dementia is constantly increasing because of the progressive aging of the population. These conditions represent a considerable challenge to patients, their family and caregivers, and the health system, because of the considerable need for resources allocation. There is no disease modifying intervention for AD and dementia, and the symptomatic pharmacological treatments has limited efficacy and considerable side effects. Non-pharmacological treatment (NPT), which includes a wide range of approaches and techniques, may play a role in the treatment of AD and dementia.
To review, with a narrative approach, current evidence on main NPTs for AD and dementia.
PubMed and the Cochrane database of systematic reviews were searched for studies written in English and published from 2000 to 2018. The bibliography of the main articles was checked to detect other relevant papers.
The role of NPT has been largely explored in AD and dementia. The main NPT types, which were reviewed here, include exercise and motor rehabilitation, cognitive rehabilitation, NPT for behavioral and psychological symptoms of dementia, occupational therapy, psychological therapy, complementary and alternative medicine, and new technologies, including information and communication technologies, assistive technology and domotics, virtual reality, gaming, and telemedicine. We also summarized the role of NPT to address caregivers' burden.
Although NPT is often applied in the multidisciplinary approach to AD and dementia, supporting evidence for their use is still preliminary. Some studies showed statistically significant effect of NPT on some outcomes, but their clinical significance is uncertain. Well-designed randomized controlled trials with innovative designs are needed to explore the efficacy of NPT in AD and dementia. Further studies are required to offer robust neurobiological grounds for the effect of NPT, and to examine its cost-efficacy profile in patients with dementia.
Di recente nell’ambito valorizzazione e dell’educazione al patrimonio culturale diverse sperimentazioni sono state indirizzate verso la definizione di nuovi paradigmi esperienziali, rimettendo al ...centro le azioni e le interazioni dei e tra i soggetti coinvolti. Si è così rinnovato l’interesse per quelle esperienze capaci di integrare educazione e divertimento, perché l’ambiente emozionale del gioco e il metodo “imparare facendo” facilita i processi di apprendimento. In questo contesto è presentata l’esperienza The Esquilino Tales, condotta nel Master in Comunicazione dei Beni Culturali della Sapienza Università di Roma, che si è proposta di valorizzare la complessità molteplice, eppure identitaria, dell’Esquilino, XV Rione di Roma. Trattandosi di un Bene in cui sia l’insieme e sia le singole sue parti sono innanzitutto riconoscibili in quanto “figure”, si è partiti dal convincimento che una proposta efficace non potesse che muovere dalla specificità segnica dei luoghi. La sperimentazione ha perciò approfondito le pratiche della Rappresentazione, innovandole attraverso le tecniche dello storytelling, della gamification e dello storydoing, con l’obiettivo di mettere a punto, all’interno di un’ampia gamma di linguaggi grafico-visuali, una strategia di comunicazione. Strategia che si è proposta di attivare tra i visitatori/cittadini e Esquilino/città modalità attive di esplorazione quali prime azioni di valorizzazione e di rigenerazione urbana da cui partire per il riscatto delle nostre città.
Purpose Delayed intensification (DI) is an integral part of treatment of childhood acute lymphoblastic leukemia (ALL), but it is associated with relevant toxicity. Therefore, standard-risk patients ...of trial AIEOP-BFM ALL 2000 (Combination Chemotherapy Based on Risk of Relapse in Treating Young Patients With ALL) were investigated with the specific aim to reduce treatment intensity. Patients and Methods Between July 2000 and July 2006, 1,164 patients (1 to 17 years of age) with standard-risk ALL (defined as the absence of high-risk cytogenetics and undetectable minimal residual disease on days 33 and 78) were randomly assigned to either experimental reduced-intensity DI (protocol III; P-III) or standard DI (protocol II; P-II). Cumulative drug doses of P-III were reduced by 30% for dexamethasone and 50% for vincristine, doxorubicin, and cyclophosphamide, which shortened the treatment duration from 49 to 29 days. The study aimed at noninferiority of reduced-intensity P-III; analyses were performed according to treatment given. Results For P-III and P-II, respectively, the 8-year rate of disease-free survival (± SE) was 89.2 ± 1.3% and 92.3 ± 1.2% ( P = .04); cumulative incidence of relapse, 8.7 ± 1.2% and 6.4 ± 1.1% ( P = .09); and overall survival, 96.1 ± 0.8% and 98.0 ± 0.6% ( P = .06). Patients with ETV6-RUNX1-positive ALL and patients 1 to 6 years of age performed equally well in both arms. The incidence of death during remission was comparable, which indicates equivalent toxicity. The 8-year cumulative incidence rate of secondary malignancies was 1.3 ± 0.5% and 0.6 ± 0.4% for P-III and P-II, respectively ( P = .37). Conclusion Although the criteria used for the standard-risk definition in this trial identified patients with exceptionally good prognosis, reduction of chemotherapy was not successful mainly because of an increased rate of relapse. The data suggest that treatment reduction is feasible in specific subgroups, which underlines the biologic heterogeneity of this cohort selected according to treatment response.
Tumor-associated macrophages (TAMs) are correlated with the progression of prostatic adenocarcinoma (PCa). The mechanistic basis of this correlation and therapeutic strategies to target TAMs in PCa ...remain poorly defined. Here, single-cell RNA sequencing was used to profile the transcriptional landscape of TAMs in human PCa, leading to identification of a subset of macrophages characterized by dysregulation in transcriptional pathways associated with lipid metabolism. This subset of TAMs correlates positively with PCa progression and shorter disease-free survival and is characterized by an accumulation of lipids that is dependent on Marco. Mechanistically, cancer cell-derived IL-1β enhances Marco expression on macrophages, and reciprocally, cancer cell migration is promoted by CCL6 released by lipid-loaded TAMs. Moreover, administration of a high-fat diet to tumor-bearing mice raises the abundance of lipid-loaded TAMs. Finally, targeting lipid accumulation by Marco blockade hinders tumor growth and invasiveness and improves the efficacy of chemotherapy in models of PCa, pointing to combinatorial strategies that may influence patient outcomes.
The pandemic is posing an occupational stressor for law enforcement personnel. Therefore, a high priority is the need to quantify this phenomenon and put supportive programs in place. During the ...pandemic period, the Italian State Police implemented different support programs for the personnel. These included a national toll-free number to provide information on COVID-19 to police staff, availability of a health care service by doctors and nurses at the national level, vaccination services, working remotely, and a psychological intervention protocol called "Together we can" ("Insieme Possiamo"). Our study firstly aims to perform a descriptive analysis of the suicide in the Italian police from 2016 to 2021, and secondly aims to compare the pandemic and pre-pandemic periods. During the SARS-CoV-2 pandemic (February 2020 to October 2021), the suicide rate in the State Police did not significantly increase compared to the pre-pandemic period, showing a stable trend with a not significant decrease in the suicide rate. The implementation of staff support services by the Central Directorate of Health of the Italian State Police and individual resilience aspects of the Police personnel in response to the pandemic may have positively affected the phenomenon. These aspects pave the way to further studies on the issue to improve preventive strategies.
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