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Pyoderma gangrenosum (PG) is a rare and complex neutrophilic dermatosis characterized by the rapid onset of painful ulcers with undermined margins and peripheral erythema. This review focuses on the emerging role of biologic therapies in the management of PG. We systematically analyzed studies, highlighting the efficacy, safety, and clinical applications of biologic agents. Despite limited randomized controlled trials, biologics like infliximab and adalimumab show promising results, particularly in refractory cases. In addition, emerging evidence supports the role of non‐TNF agents such as IL‐1, IL‐17, IL‐23, and IL‐36 inhibitors, as well as JAK inhibitors, expanding the therapeutic armamentarium for refractory PG. Further research is essential to establish standardized guidelines for their use.

Many adalimumab biosimilars have been approved for the same indications as their originator (Humira ). However, data on their efficacy and safety in children with psoriasis are scarce. To assess the effectiveness and safety of adalimumab biosimilars in a group of adalimumab-naïve patients and another group of patients who switched from originator adalimumab to biosimilars. The co-primary endpoints were the PASI absolute mean, PASI 75, and PASI 90 at 16, 24 and 52 weeks. In this 52-week, multi-center, non-interventional, observational, retrospective study, patients starting biosimilars in routine practice after January 2022 were enrolled at 10 sites across Italy, Portugal, and France. Disease activity scores such as the Psoriasis Area Severity Index (PASI) and safety data were captured during 12 months following adalimumab biosimilar initiation. A total of 102 pediatric patients with psoriasis receiving adalimumab biosimilar therapy either as naïve (n = 72) or switching from originator adalimumab (n = 30) were enrolled. Median absolute PASI remained low at weeks 16, 24, and 52 in both groups (naïve 5.4, 4.3, 2.8; switching 2.6; 2.0; 1.4 respectively). PASI 75 response at weeks 16, 24, and 52 was observed in 41.7, 55.0, and 77.8% of patients in the naive group and 82.8%, 86.2%, and 92.6% of patients in the switch group. PASI 90 response at weeks 16, 24, and 52 was achieved by 23.3%, 26.7%, and 46.3% of patients in the naïve group and 58.6%, 65.5%, and 55.6% of patients in the switch group. Three patients discontinued biosimilars after the switch due to loss of efficacy. No emergency room visits or hospitalizations were observed during the study period and none of the patients experienced serious adverse effects. Adalimumab biosimilars showed a favorable effectiveness/safety profile in childhood psoriasis. Switching from reference adalimumab to biosimilars did not impact effectiveness and safety. A likelihood of discontinuation was noted in patients who switched from Humira to biosimilars.

Because of their isolation, biotic communities of urban green spaces are expected to be similar to those of oceanic islands. This should be particularly true for insects, which represent an important component of urban faunas. The equilibrium theory of island biogeography (ETIB) allows for the formulation of some hypotheses regarding the influence of the geographical characteristics of green spaces on insect species richness and extinction risk. Based on island biogeography principles, we present eight predictions on how green space characteristics should influence insect species richness and loss. We analysed the current literature in order to determine which predictions were supported and which were not. We found that many studies gave outcomes that support ETIB predictions about the effects of area and isolation of green spaces; we found no strong support for predictions about shape and extent of native habitat in the literature that we reviewed. Most of the available studies dealt with patterns in species richness, whereas insect species loss has been rarely investigated. Future developments in the application of island biogeography principles to urban insect conservation should address temporal trends in species persistence and the analysis of species co-occurrence and nestedness.

The pharmacological MRI (phMRI) technique is being increasingly used in both pre-clinical and clinical models to investigate pharmacological effects on task-free brain function. Ketamine, an N-methyl-d-aspartate receptor (NMDAR) antagonist, induces a strong phMRI response and represents a promising pharmacological model to investigate the role of glutamatergic abnormalities in psychiatric symptomatology. The aim of this study was to assess whether the brain response to ketamine is reliable in order to validate ketamine phMRI as a mechanistic marker of glutamatergic dysfunction and to determine its utility in repeated measures designs to detect the modulatory effect of other drugs. Thus we assessed the test–retest reliability of the brain response to ketamine in healthy volunteers and identified an optimal modelling approach with reliability as our selection criterion. PhMRI data were collected from 10 healthy male participants, at rest, on two separate occasions. Subanaesthetic doses of I.V. ketamine infusion (target plasma levels 50ng/mL and 75ng/mL) were administered in both sessions. Test–retest reliability of the ketamine phMRI response was assessed voxel-wise and on pre-defined ROIs for a range of temporal design matrices including different combinations of nuisance regressors designed to model shape variance, linear drift and head motion. Effect sizes are also reported. All models showed a significant and widespread response to low-dose ketamine in predicted cerebral networks and as expected, increasing the number of model parameters improved model fit. Reliability of the predefined ROIs differed between the different models assessed. Using reliability as the selection criterion, a model capturing subject motion and linear drift performed the best across two sessions. The anatomical distribution of effects for all models was consistent with results of previous imaging studies in humans with BOLD signal increases in regions including midline cingulate and supracingulate cortex, thalamus, insula, anterior temporal lobe and ventrolateral prefrontal structures, and BOLD signal decreases in the subgenual cingulate cortex. This study represents the first investigation of the test–retest reliability of the BOLD phMRI response to acute ketamine challenge. All models tested were effective at describing the ketamine response although the design matrix associated with the highest reliability may represent a robust and well-characterised ketamine phMRI assay more suitable for repeated-measures designs. This ketamine assay is applicable as a model of neurotransmitter dysfunction suitable as a pharmacodynamic imaging tool to test and validate modulatory interventions, as a model of NMDA hypofunction in psychiatric disorders, and may be adapted to understand potential antidepressant and analgesic effects of NMDAR antagonists.

The spatial and temporal variability of water levels was investigated across a section of floodplain in the Pantanal that represents typical geomorphic and ecological complexity of these environments. A series of 11 staff gauges were installed along a 12-km transect running perpendicularly from the Cuiabá River into the floodplain. The staff gauges were monitored fortnightly during the flood seasons from 2004 to 2007. Contrary to what is often assumed, the water surface profile was never level, and it was particularly variable when there was less water on the floodplain. Water surface slope varied from 1.4 × 10 −4 (unitless) to 1.3 × 10 −3 indicating substantial water movement that was verified by flow observations. The spatial patterns of water level variation were repeated across years, even though there was considerable interannual variation in magnitude and duration of floodplain inundation. In 2004 and 2005, the duration of inundation was 121 and 120 days, respectively, but in 2006 and 2007, inundation lasted 166 and 157 days, respectively. These observations reveal considerable small-scale spatial variability in the water surface profile, but with persistent patterns over space and time that are related to the river hydrograph and the channels that convey flood waters across the area. This study contributes to our understanding of inundation hydrology and its linkages to ecosystem processes, and additionally provides a valuable data set for calibration and validation of remote sensing approaches to measurement of inundation area and water movement across floodplains.

Genetic diversity is one of the most important issues in studies on conservation of cattle breeds and endangered species. The objective of this study was to estimate the levels of genetic differentiation between locally adapted taurine ( Bos taurus taurus ) and zebu ( Bos taurus indicus ) breeds in Brazil, which were genotyped for more than 777,000 SNPs. The fixation index ( F ST ), principal component analysis (PCA), and Bayesian clustering were estimated. The F ST highlighted genetic differentiation between taurine and zebu breeds. The taurine lines, Caracu and Caracu Caldeano, had significant genetic differentiation ( F ST close to 5%) despite their recent selection for different uses (meat and milk). This genetic variability can be used for conservation of locally adapted animals, as well as for breeding programs on zebu breeds. Introgression of zebu in locally adapted breeds was identified, especially in Curraleiro Pé-Duro breed. The Gyr breed, however, had low breed purity at genomic level due to its very heterogeneous mixing pattern.

Purpose To investigate plasma and cerebrospinal fluid (CSF) concentrations of pentraxin 3 (PTX3), a prototypic long pentraxin protein induced by proinflammatory signals, in subarachnoid hemorrhage (SAH), and its relation with SAH-associated vasospasm. Methods Serial plasma and CSF samples were collected from 38 consecutive SAH patients admitted to the Neurosurgical Intensive Care. PTX3 concentrations were analyzed in relation to clinical status and clinical vasospasm (defined as neuro-worsening and angiographic confirmation of vessel narrowing). Since neutrophils are an important source of preformed PTX3, myeloperoxidase (MPO) in CSF was measured to assess the correlation with CSF PTX3 and establish whether blood contamination was the determinant of PTX3 increase. Results PTX3 was elevated in all SAH patients both in plasma and CSF. Acute peak (first 48 h after SAH) CSF PTX3 was significantly higher in patients who later developed vasospasm [median 13.6 (range 2.3–51.9) ng/ml] compared to those who did not [3.2 (0.1–50.5) ng/ml, p  = 0.03]. The temporal pattern of CSF PTX3 in patients with vasospasm was triphasic with a peak during the first 48 h after SAH, a subsequent decrease in the following 48–96 h and a secondary significant increase with the occurrence of vasospasm. A loose correlation between CSF PTX3 and MPO was observed ( r 2  = 0.13), indicating that following SAH there is a brain production of PTX3. Conclusions Acute increased concentrations of PTX3 in CSF but not in plasma are related to the occurrence of vasospasm, indicating that measurement of CSF PTX3 associated with the clinical evaluation can improve early diagnosis of this complication.

Primary proinflammatory cytokines, such as IL-1 β , play a crucial pathogenic role in multiple sclerosis and its animal model experimental autoimmune encephalomyelitis (EAE), and may represent, therefore, a suitable therapeutic target. We have previously established the delivery of anti-inflammatory cytokine genes within the central nervous system (CNS), based on intracisternal (i.c.) injection of non-replicative HSV-1-derived vectors. Here we show the therapeutic efficacy of i.c. administration of an HSV-1-derived vector carrying the interleukin-1receptor antagonist (IL-1ra) gene, the physiological antagonist of the proinflammatory cytokine IL-1, in C57BL/6 mice affected by myelin oligodendrocyte glycoprotein-induced EAE. IL-1ra gene therapy is effective preventively, delaying EAE onset by almost 1 week (22.4±1.4 days post-immunization vs 15.9±2.1 days in control mice; P =0.0229 log-rank test), and decreasing disease severity. Amelioration of EAE course was associated with a reduced number of macrophages infiltrating the CNS and in a decreased level of proinflammatory cytokine mRNA in the CNS, suggesting an inhibitory activity of IL-1ra on effector cell recruitment, as antigen-specific peripheral T-cell activation and T-cell recruitment to the CNS is unaffected. Thus, local IL-1ra gene therapy may represent a therapeutic alternative for the inhibition of immune-mediated demyelination of the CNS.