Phase diagram mapping is a useful method for predicting and rationalizing unusual thermally and mechanically triggered crystal transition phenomena. Here we focus on crystals of pimelic acid, which ...is known to exist as at least three polymorphs: modifications I–III. Modification III exhibits twinning ferroelasticity and a polymorphic transition, involving superelastic behavior by shearing. Additionally, a phase transition from modification III to modification II by heating involves a rapid expansion of crystals. The reverse transition from the metastable modification II to the thermally stable modification III at ambient temperature by mechanical stimuli involves rapid shrinkage, causing crystals to jump or rapidly fragment. For the first time a comprehensive phase diagram has been presented that accounts for the three different mechanical responses observed for pimelic acid: jumping/fragmentation, superelasticity, and ferroelasticity. Both thermal and mechanical transitions have been rationally mapped on the phase diagram.
Twenty-five intervention studies were meta-analytically examined regarding the effect of including relatives in schizophrenia treatment. The studies investigated family intervention programs to ...educate relatives and help them cope better with the patient's illness. The patient's relapse rate, measured by either a significant worsening of symptoms or rehospitalization in the first years after hospitalization, served as the main study criterion. The main result of the meta-analysis was that the relapse rate can be reduced by 20 percent if relatives of schizophrenia patients are included in the treatment. If family interventions continued for longer than 3 months, the effect was particularly marked. Furthermore, different types of comprehensive family interventions have similar results. The bifocal approach, which offers psychosocial support to relatives and schizophrenia patients in addition to medical treatment, was clearly superior to the medication-only standard treatment. The effects of family interventions and comprehensive patient interventions were comparable, but the combination did not yield significantly better results than did a treatment approach, which focused on either the patient or the family. This meta-analysis indicates that psychoeducational interventions are essential to schizophrenia treatment.
Attention-deficit hyperactivity disorder (ADHD) is increasingly recognized not only in children but also in adults. Neuropsychological tests are important tools to quantify the attentional and/or ...cognitive deficits of patients compared to controls. The present meta-analysis integrates 24 empirical studies reporting results of at least one of 50 standard neuropsychological tests comparing adult ADHD patients with controls. The 50 tests were categorized into the following 10 functional domains: verbal ability, figural problem solving, abstract problem solving, executive function, fluency, simple attention, sustained attention, focused attention, verbal memory, figural memory. For each domain a pooled effect size
d′ was calculated. Complex attention variables and verbal memory discriminated best between ADHD patients and controls. Effect sizes for these domains were homogeneous and of moderate size (
d′ between 0.5 and 0.6). In contrast to results reported in children, executive functions were not generally reduced in adult ADHD patients.
Abstract The Positive and Negative Syndrome Scale (PANSS) and the Brief Psychiatric Rating Scale (BPRS) are the most frequently used scales to rate the symptoms of schizophrenia. There are many ...situations in which it is important to know what a given total score or a percent reduction from baseline score of one scale means in terms of the other scale. We used the equipercentile linking method to identify corresponding scores of simultaneous BPRS and PANSS ratings in 3767 patients from antipsychotic drug trials. Data were collected at baseline and at weeks 1, 2, 4 and 6. BPRS total scores of 18, 30, 40 and 50 roughly corresponded to PANSS total scores of 31, 55, 73 and 90, respectively. An absolute BPRS improvement of 10, 20, 30, 40 points corresponded to a PANSS improvement of 15, 32, 50, and 67. A percentage improvement of the BPRS total score from baseline of 19%, 30%, 40% and 50% roughly corresponded to percentage PANSS improvement of 16%, 25%, 35%, and 44%. Thus a given PANSS percent improvement was always lower than the corresponding BPRS percent improvement, on the average by 4–5%. A reason may be the higher number of items used in the PANSS. These results are important for the comparison of trials that used these rating scales. We present a detailed conversion table in an online supplement.
A non‐interpenetrated metal–organic framework with a paddle‐wheel secondary building unit has been activated by direct thermal evacuation, guest exchange with a volatile solvent, and supercritical ...CO2 drying. Conventional thermal activation yields a mixture of crystalline phases and some amorphous content. Exchange with a volatile solvent prior to vacuum activation produces a pure breathing phase with high sorption capacity, selectivity for CO2 over N2 and CH4, and substantial hysteresis. Supercritical drying can be used to access a guest‐free open phase. Pressure‐resolved differential scanning calorimetry was used to confirm and investigate a systematic loss of sorption capacity by the breathing phase as a function of successive cycles of sorption and desorption. A corresponding loss of sample integrity was not detectable by powder X‐ray diffraction analysis. This may be an important factor to consider in cases where flexible MOFs are earmarked for industrial applications.
Taking a deep breath: A metal–organic framework with a paddle‐wheel secondary building unit is activated by direct thermal evacuation, guest exchange with a volatile solvent, and supercritical CO2 drying. The solvent exchange step produces a pure breathing phase with high sorption capacity, selectivity for CO2 over N2 and CH4, and substantial hysteresis.
Age-related macular degeneration (AMD) is the most prevalent cause of blindness in the elderly, and its exsudative subtype critically depends on local production of vascular endothelial growth factor ...A (VEGF). Mononuclear phagocytes, such as macrophages and microglia cells, can produce VEGF. Their precursors, for example monocytes, can be recruited to sites of inflammation by the chemokine receptor CCR2, and this has been proposed to be important in AMD. To investigate the role of macrophages and CCR2 in AMD, we studied intracellular VEGF content in a laser-induced murine model of choroidal neovascularisation. To this end, we established a technique to quantify the VEGF content in cell subsets from the laser-treated retina and choroid separately. 3 days after laser, macrophage numbers and their VEGF content were substantially elevated in the choroid. Macrophage accumulation was CCR2-dependent, indicating recruitment from the circulation. In the retina, microglia cells were the main VEGF+ phagocyte type. A greater proportion of microglia cells contained VEGF after laser, and this was CCR2-independent. On day 6, VEGF-expressing macrophage numbers had already declined, whereas numbers of VEGF+ microglia cells remained increased. Other sources of VEGF detectable by flow cytometry included in dendritic cells and endothelial cells in both retina and choroid, and Müller cells/astrocytes in the retina. However, their VEGF content was not increased after laser. When we analyzed flatmounts of laser-treated eyes, CCR2-deficient mice showed reduced neovascular areas after 2 weeks, but this difference was not evident 3 weeks after laser. In summary, CCR2-dependent influx of macrophages causes a transient VEGF increase in the choroid. However, macrophages augmented choroidal neovascularization only initially, presumably because VEGF production by CCR2-independent eye cells prevailed at later time points. These findings identify macrophages as a relevant source of VEGF in laser-induced choroidal neovascularization but suggest that the therapeutic efficacy of CCR2-inhibition might be limited.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cardioprotection by salvage of the infarct-affected myocardium is an unmet yet highly desired therapeutic goal. To develop new dedicated therapies, experimental myocardial ischemia/reperfusion (I/R) ...injury would require methods to simultaneously characterize extent and localization of the damage and the ensuing inflammatory responses in whole hearts over time. Here we present a three-dimensional (3D), simultaneous quantitative investigation of key I/R injury-components by combining bleaching-augmented solvent-based non-toxic clearing (BALANCE) using ethyl cinnamate (ECi) with light sheet fluorescence microscopy. This allows structural analyses of fluorescence-labeled I/R hearts with exceptional detail. We discover and 3D-quantify distinguishable acute and late vascular I/R damage zones. These contain highly localized and spatially structured neutrophil infiltrates that are modulated upon cardiac healing. Our model demonstrates that these characteristic I/R injury patterns can detect the extent of damage even days after the ischemic index event hence allowing the investigation of long-term recovery and remodeling processes.
The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that ...three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C− macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C+ macrophages. Such Ly6C+ macrophages played a previously undescribed helper role: once recruited to the site of infection, they produced the cytokine TNF, which caused Ly6C− macrophages to secrete CXCL2. This chemokine activated matrix metalloproteinase-9 in neutrophils, allowing their entry into the uroepithelium to combat the bacteria. In summary, the sentinel macrophages elicit the powerful antibacterial functions of neutrophils only after confirmation by the helper macrophages, reminiscent of the licensing role of helper T cells in antiviral adaptive immunity. These findings identify helper macrophages and TNF as critical regulators in innate immunity against bacterial infections in epithelia.
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•Neutrophils, Ly6C− and Ly6C+ macrophages perform distinct antibacterial functions•Ly6C+ macrophages act as innate immune helper cells in antibacterial defense•TNF is the innate helper factor; it permits neutrophil migration into epithelium•Distinct CXCR2 ligands mediate endothelial and epithelial neutrophil migration
In urinary tract infection, neutrophils are recruited from the blood to the infected organ by tissue-resident sentinel macrophages but are only directed to the frontline, the uroepithelium, after receiving a confirmation signal from recruited helper macrophages
Worldwide marine invaders, such as the brown alga Undaria pinnatifida, offer challenging models for unraveling the apparent paradox of sustainable settlement of exotic species over a large spectrum ...of environments. Two intergenic noncoding mitochondrial loci were found to be highly informative at the within-species level. Twenty-five haplotypes were found over the whole dataset (333 base pairs, 524 individuals, and 24 populations). The native range showed striking population genetic structure stemming from low diversity within and high differentiation among populations, a pattern not observed in the introduced range of this seaweed. Contrary to classical expectations of founding effects associated with accidental introduction of exotic species, most of the introduced populations showed high genetic diversity. At the regional scale, genetic diversity and sequence divergence showed contrasting patterns in the two main areas of introduction (Europe and Australasia), suggesting different processes of introduction in the two regions. Gene genealogy analyses point to aquaculture as a major vector of introduction and spread in Europe but implicate maritime traffic in promoting recurrent migration events from the native range to Australasia. The multiplicity of processes and genetic signatures associated with the successful invasion confirms that multiple facets of global change, e.g., aquaculture practices, alteration of habitats, and increased traffic, act in synergy at the worldwide level, facilitating successful pandemic introductions.
A dense network of macrophages and dendritic cells (DC) expressing the chemokine receptor CX3CR1 populates most tissues. We recently reported that CX3CR1 regulates the abundance of CD11c(+) DC in the ...kidney and thereby promotes renal inflammation in glomerulonephritis. Given that chronic inflammation usually causes fibrosis, we hypothesized that CX3CR1 deficiency should attenuate renal fibrosis. However, when we tested this hypothesis using the DC-independent murine fibrosis model of unilateral ureteral obstruction, kidney fibrosis was unexpectedly more severe, despite less intrarenal inflammation. Two-photon imaging and flow cytometry revealed in kidneys of CX3CR1-deficient mice more motile Ly6C/Gr-1(+) macrophages. Flow cytometry verified that renal macrophages were more abundant in the absence of CX3CR1 and produced more of the key profibrotic mediator, TGF-β. Macrophages accumulated because of higher intrarenal proliferation, despite reduced monocyte recruitment and higher signs of apoptosis within the kidney. These findings support the theory that tissue macrophage numbers are regulated through local proliferation and identify CX3CR1 as a regulator of such proliferation. Thus, CX3CR1 inhibition should be avoided in DC-independent inflammatory diseases because it may promote fibrosis.