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Cultures in Mediterranean climate zones (MCZs) around the world have long been reliant on groundwater and springs as freshwater sources. While their ecology and cultural sustainability are recognized as critically important, inter-relationships between springs and culture in MCZs have received less attention. Here we augmented a global literature review with case studies in MCZ cultural landscapes to examine the diversity and intensity of cultural and socio-economic relationships on spring ecohydrogeology. MCZs are often oriented on western and southern coasts in tectonically active landscapes which control aquifer structure, the prevalence of westerly winds, and aridity, and generally expose associated habitats and cultures to harsh afternoon sunlight. Cultural appreciation and appropriation of springs ranges widely, from their use as subsistence water supplies to their roles in profound traditions such as Greco-Roman nymphalea as well as Asian and Abrahamic spiritual cleansing and baptism. The abandonment of traditional ways of life, such as rural livestock production, for urban ones has shifted impacts on aquifers from local to regional groundwater exploitation. The commoditization of water resources for regional agricultural, industrial (e.g., mining, water bottling, geothermal resorts), and urban uses is placing ever-increasing unsustainable demands on aquifers and spring ecosystems. When the regional economic value of springs approaches or exceeds local cultural values, these irreplaceable aquatic ecosystems are often degraded, over-looked, and lost. Sustainable stewardship of springs and the aquifers that support them is a poorly recognized but central conservation challenge for modern Mediterranean societies as they face impending impacts of global climate change. Solutions to this crisis require education, societal dialogue, and improved policy and implementation.

Post-transplantation cyclophosphamide (PTCy) has decreased GVHD incidence. Endothelial damage in allo-HCT is caused by multiple factors, including conditioning treatments and some immunosupressants, and underlies HCT-complications as GVHD. Nevertheless, the specific impact of PTCy on the endothelium remains unclear. We evaluated the effect of mafosfamide (MAF), an active Cy analog, on endothelial cells (ECs) vs. cyclosporine A (CSA), with known damaging endothelial effect. ECs were exposed to MAF and CSA to explore changes in endothelial damage markers: (i) surface VCAM-1, (ii) leukocyte adhesion on ECs, (iii) VE-cadherin expression, (iv) production of VWF, and (v) activation of intracellular signaling proteins (p38MAPK, Akt). Results obtained (expressed in folds vs. controls) indicate that both compounds increased VCAM-1 expression (3.1 ± 0.3 and 2.8 ± 0.6, respectively, p < 0.01), with higher leukocyte adhesion (5.5 ± 0.6, p < 0.05, and 2.8 ± 0.4, respectively). VE-cadherin decreased with MAF (0.8 ± 0.1, p < 0.01), whereas no effect was observed with CSA. Production of VWF augmented with CSA (1.4 ± 0.1, p < 0.01), but diminished with MAF (0.9 ± 0.1, p < 0.05). p38MAPK activation occurred with both compounds, being more intense and faster with CSA. Both drugs activated Akt, with superior MAF effect at longer exposure. Therefore, the cyclophosphamide analog MAF is not exempt from a proinflammatory effect on the endothelium, though without modifying the subendothelial characteristics.

¿Cómo pueden ser más inteligentes las ciudades? ofrece al lector una breve selección de estudios de caso representativos de los contenidos de la especialización Ciudades más inteligentes y ciudadanía, del programa Ciudad y Urbanismo de la Universitat Oberta de Catalunya.Tratamos los grandes temas relacionados con la ciudad –transformaciones y estrategias urbanas, gobierno, innovación en la gestión pública, nueva economía urbana y la mundialización de la cultura– como la base imprescindible para todos aquellos que quieran actuar en la ciudad desde sus multiples dimensiones.El objetivo es aportar conocimientos teóricos transversales, así como instrumentos y métodos utilizados para gestionar y promover ciudades más inteligentes.

The HER2-enriched (HER2-E) subtype within HER2-positive (HER2+) breast cancer is highly addicted to the HER2 pathway. However, ∼20–60% of HER2+/HER2-E tumors do not achieve a complete response following anti-HER2 therapies. Here we evaluate gene expression data before, during and after neoadjuvant treatment with lapatinib and trastuzumab in HER2+/HER2-E tumors of the PAMELA trial and breast cancer cell lines. Our results reveal that dual HER2 blockade in HER2-E disease induces a low-proliferative Luminal A phenotype both in patient’s tumors and in vitro models. These biological changes are more evident in hormone receptor-positive (HR+) disease compared to HR-negative disease. Interestingly, increasing the luminal phenotype with anti-HER2 therapy increased sensitivity to CDK4/6 inhibition. Finally, discontinuation of HER2-targeted therapy in vitro, or acquired resistance to anti-HER2 therapy, leads to restoration of the original HER2-E phenotype. Our findings support the use of maintenance anti-HER2 therapy and the therapeutic exploitation of subtype switching with CDK4/6 inhibition. HER2-enriched breast cancers within the HER2-positive subtype are addicted to the HER2 pathway. Here, the authors analyse gene expression before, during, and after treatment with anti-HER2-based therapies in the phase II PAMELA clinical trial, finding phenotypic changes induced by treatment.

Time-to-fall off an accelerating rotating rod (rotarod) is widely utilized to evaluate rodent motor performance. We reasoned that this simple outcome could be refined with additional measures explicit in the task (however inconspicuously) to examine what we call movement sub-structure. Our goal was to characterize normal variation or motor impairment more robustly than by using time-to-fall. We also hypothesized that measures (or features) early in the sub-structure could anticipate the learning expected of a mouse undergoing serial trials. Using normal untreated and baclofen-treated movement-impaired mice, we defined these features and automated their analysis using paw video-tracking in three consecutive trials, including paw location, speed, acceleration, variance and approximate entropy. Spectral arc length yielded speed and acceleration uniformity. We found that, in normal mice, paw movement smoothness inversely correlated with rotarod time-to-fall for the three trials. Greater approximate entropy in vertical movements, and opposite changes in horizontal movements, correlated with greater first-trial time-to-fall. First-trial horizontal approximate entropy in the first few seconds predicted subsequent time-to-fall. This allowed for the separation, after only one rotarod trial, of different-weight, untreated mouse groups, and for the detection of mice otherwise unimpaired after baclofen, which displayed a time-to-fall similar to control. A machine-learning support vector machine classifier corroborated these findings. In conclusion, time-to-fall off a rotarod correlated well with several measures, including some obtained during the first few seconds of a trial, and some responsive to learning over the first two trials, allowing for predictions or preemptive experimental manipulations before learning completion.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disease of the peripheral nerves characterized by proximal and distal muscle weakness and sensory abnormalities. CIDP has been associated with various pathophysiological mechanisms that are not fully understood and that likely differ across groups of patients. It has been proposed that an interplay of different immunopathological mechanisms including the cellular, humoral and complement pathways play a key role in peripheral nerve damage in CIDP. Currently approved treatments and therapies in research often target different potential pathophysiological mechanisms. The efficacy of these different treatments can shed light on the prominence of particular pathophysiological pathways in subsets of patients with CIDP. For example, the complement pathway plays a key role in promoting macrophage-mediated demyelination, and complement inhibitors are under development as new targets in CIDP treatment, with mixed results. The neonatal Fc receptor (FcRn) has also been targeted as a promising treatment avenue due to its role in immunoglobulin G degradation. Efgartigimod is the first FcRn blocker approved for the treatment of CIDP. This review provides an overview of key proposed mechanisms of action in CIDP pathophysiology in the context of both basic scientific findings and treatment targets in recent clinical studies.

Background and purpose The purpose was to perform a nationwide epidemiological study of Guillain–Barré syndrome (GBS) in Spain, analysing background incidences and seasonal variation and trying to identify incidence changes during the coronavirus disease 2019 (COVID‐19) years. Methods This was an observational study collecting all GBS diagnoses from the National Epidemiological Surveillance Network collected by the Ministry of Health. Patients discharged with GBS as the main diagnosis and admitted during 2018–2021 were included. Data on the incidence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections were obtained from the National Epidemiology Centre. Results In total, 3147 cases were included, 832 in 2018, 861 in 2019, 670 in 2020 and 784 in 2021. Nationwide hospital incidence was 1.78 in 2018, 1.71 in 2019, 1.41 in 2020 and 1.66 in 2021, with an increased frequency in males, the elderly population and in the winter season. Eleven per cent of GBS patients needed ventilatory support. GBS and SARS‐CoV‐2 incidences did not correlate with one another (r = −0.29, p = 0.36). GBS incidence decreased during 2020 and during the COVID‐19 lockdown period in comparison to the same months of 2018–2019. Conclusions The incidence of GBS in Spain is similar to that of other countries. Despite prior reports describing a significant increase in COVID‐19‐associated GBS in Spain, a significant drop of GBS incidence during the SARS‐CoV‐2 pandemic was detected, probably due to prevention measures.

Background The clinical status and treatment response of patients with peripheral neuropathies (PNs) rely on subjective and inaccurate clinical scales. Wearable sensors have been evaluated successfully in other neurological conditions to study gait and balance. Our aim was to explore the ability of biomechanical analysis using wearable technology to monitor disease activity in PN. Methods We conducted a single-center, longitudinal study to analyze gait parameters in PN patients and healthy controls using wearable biomechanical sensors. We used a novel technology that registers and integrates data from multiple wearable inertial sensors placed at different locations and plantar insoles. This system allows measuring kinematics, spatio-temporal parameters and plantar pressure. Patients wore the wearable system while performing the 2-min walking test (2MWT). Results We included 37 chronic inflammatory demyelinating polyneuropathy (CIDP) patients, 3 chronic ataxic neuropathy, ophthalmoplegia, immunoglobulin M [IgM] paraprotein (CANOMAD) patients, 21 monoclonal gammopathy patients of undetermined significance associated with IgM (IgM-MGUS) patients, 7 patients with autoimmune nodopathies, 11 patients with hereditary neuropathies, and 50 healthy controls. First, we analyzed the sensor's ability to detect changes in ataxia and steppage gait severity and found significant differences in spatiotemporal and angular variables of the gait cycle. Second, we found correlations between biomechanical features and clinical scales and with the specific gait phenotype they associated with. Finally, we demonstrated that this technology is able to capture clinically significant changes in gait features over time. Conclusions Our study provides proof-of-concept that wearable technology effectively detects and grades gait impairment, captures clinically relevant changes, and could enhance gait assessment in routine care and clinical research for patients with PN.