Characterizing historical transformation trajectories of the forest landscape in Rome's metropolitan area (Italy) for effective planning of sustainability goals

With the aim at developing a landscape dynamics framework for environmental planning and management and testing the effectiveness of protected areas in achieving the 2030 Agenda of the United Nations sustainability goals, we characterized the historical transformation trajectories of forest area changes from 1936 to 2010 in the Metropolitan City of Rome Capital (Italy). Remote sensing-based products coupled with landscape pattern metrics and fragmentation analysis have been implemented, comparing different historical forest maps. The results show a remarkable forest area gain – from 17.6% to 25.5% – thanks to 68,299 ha of recently established forest. Statistical descriptors showed that the highest relative gain occurred in mountain zones, confirming a wide European forest recovery pattern in marginal areas from past deforestation and overexploitation. Deforestation mainly occurred in the flat and hilly areas where almost 26,000 ha of forests were lost since 1936. In summary, two main forest landscape dynamics were reconstructed: (I) the increase of forest cover fragmentation in the lowland areas; and (II) the rise in the forest area in the interior sectors of the mountain landscape, mainly within protected areas. Restoring the forest ecosystem's bioecological integrity has been highlighted as an urgent action for biodiversity conservation and carbon mitigation. In lowland areas, the study revealed the urgent need to establish new protected areas and rewilding spaces as landscape metrics are relatively below the sustainability targets for healthy forest ecosystems. The proposed framework can be used for testing the effectiveness of environmental planning and management in other forest landscapes to achieve the Agenda 2030 goals

Cognitive disabilities and bioethical implications in down syndrome

Down syndrome is a genetic syndrome related to trisomy 21, and characterized by intellectual and adaptive deficiencies, facial deformities, cardiopathiacenitis and hypotonia that determine a specific cognitive behavioral phenotype. The behavioral and psychiatric cognitive phenotype and its evolutionary profile impose bioethical considerations in the down to promote better and personalized clinical and relief, diagnostic and therapeutic strategies to favor an adequate insertion of the down in the scholastic and work environment

Gestational oxidative stress protects against adult obesity and insulin resistance

Pregnancy complications such as preeclampsia cause increased fetal oxidative stress and fetal growth restriction, and associate with a higher incidence of adult metabolic syndrome. However, the pathophysiological contribution of oxidative stress per se is experimentally difficult to discern and has not been investigated. This study determined, if increased intrauterine oxidative stress (IUOx) affects adiposity, glucose and cholesterol metabolism in adult Ldlr-/-xSod2+/+ offspring from crossing male Ldlr-/-xSod2+/+ mice with Ldlr-/-xSod2+/- dams (IUOx) or Ldlr-/-xSod2+/- males with Ldlr-/-xSod2+/+ dams (control). At 12 weeks of age mice received Western diet for an additional 12 weeks. Adult male IUOx offspring displayed lower body weight and reduced adiposity associated with improved glucose tolerance compared to controls. Reduced weight gain in IUOx was conceivably due to increased energy dissipation in white adipose tissue conveyed by higher expression of Ucp1 and an accompanying decrease in DNA methylation in the Ucp1 enhancer region. Female offspring did not show comparable phenotypes. These results demonstrate that fetal oxidative stress protects against the obesogenic effects of Western diet in adulthood by programming energy dissipation in white adipose tissue at the level of Ucp1

From intensive care to step-down units: Managing patients throughput in response to COVID-19

Quality problem or issue: The on-going COVID-19 pandemic may cause the collapse of healthcare systems because of unprecedented hospitalization rates. Initial assessment: A total of 8.2 individuals per 1000 inhabitants have been diagnosed with COVID-19 in our province. The hospital predisposed 110 beds for COVID-19 patients: On the day of the local peak, 90% of them were occupied and intensive care unit (ICU) faced unprecedented admission rates, fearing system collapse. Choice of solution: Instead of increasing the number of ICU beds, the creation of a step-down unit (SDU) close to the ICU was preferred: The aim was to safely improve the transfer of patients and to relieve ICU from the risk of overload. Implementation: A nine-bed SDU was created next to the ICU, led by intensivists and ICU nurses, with adequate personal protective equipment, monitoring systems and ventilators for respiratory support when needed. A second six-bed SDU was also created. Evaluation: Patients were clinically comparable to those of most reports from Western Countries now available in the literature. ICU never needed supernumerary beds, no patient died in the SDU, and there was no waiting time for ICU admission of critical patients. SDU has been affordable from human resources, safety and economic points of view. Lessons learned: COVID-19 is like an enduring mass casualty incident. Solutions tailored on local epidemiology and available resources should be implemented to preserve the efficiency and adaptability of our institutions and provide the adequate sanitary response

Aptamer-Mediated Delivery of Splice-Switching Oligonucleotides to the Nuclei of Cancer Cells

To reduce the adverse effects of cancer therapies and increase their efficacy, new delivery agents that specifically target cancer cells are needed. We and others have shown that aptamers can selectively deliver therapeutic oligonucleotides to the endosome and cytoplasm of cancer cells that express a particular cell surface receptor. Identifying a single aptamer that can internalize into many different cancer cell-types would increase the utility of aptamer-mediated delivery of therapeutic agents. We investigated the ability of the nucleolin aptamer (AS1411) to internalize into multiple cancer cell types and observed that it internalizes into a wide variety of cancer cells and migrates to the nucleus. To determine if the aptamer could be utilized to deliver therapeutic oligonucleotides to modulate events in the nucleus, we evaluated the ability of the aptamer to deliver splice-switching oligonucleotides. We observed that aptamer-splice-switching oligonucleotide chimeras can alter splicing in the nuclei of treated cells and are effective at lower doses than the splice switching oligonucleotides alone. Our results suggest that aptamers can be utilized to deliver oligonucleotides to the nucleus of a wide variety of cancer cells to modulate nuclear events such as RNA splicing

Thrombosis Is Reduced by Inhibition of COX-1, but Unaffected by Inhibition of COX-2, in an Acute Model of Platelet Activation in the Mouse

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Early Induction of Oxidative Stress in Mouse Model of Alzheimer Disease with Reduced Mitochondrial Superoxide Dismutase Activity

While oxidative stress has been linked to Alzheimer's disease, the underlying pathophysiological relationship is unclear. To examine this relationship, we induced oxidative stress through the genetic ablation of one copy of mitochondrial antioxidant superoxide dismutase 2 (Sod2) allele in mutant human amyloid precursor protein (hAPP) transgenic mice. The brains of young (5–7 months of age) and old (25–30 months of age) mice with the four genotypes, wild-type (Sod2+/+), hemizygous Sod2 (Sod2+/−), hAPP/wild-type (Sod2+/+), and hAPP/hemizygous (Sod2+/−) were examined to assess levels of oxidative stress markers 4-hydroxy-2-nonenal and heme oxygenase-1. Sod2 reduction in young hAPP mice resulted in significantly increased oxidative stress in the pyramidal neurons of the hippocampus. Interestingly, while differences resulting from hAPP expression or Sod2 reduction were not apparent in the neurons in old mice, oxidative stress was increased in astrocytes in old, but not young hAPP mice with either Sod2+/+ or Sod2+/−. Our study shows the specific changes in oxidative stress and the causal relationship with the pathological progression of these mice. These results suggest that the early neuronal susceptibility to oxidative stress in the hAPP/Sod2+/− mice may contribute to the pathological and behavioral changes seen in this animal model

Elevated Ratio of Urinary Metabolites of Thromboxane and Prostacyclin Is Associated with Adverse Cardiovascular Events in ADAPT

Results from prevention trials, including the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT), have fueled discussion about the cardiovascular (CV) risks associated with non-steroidal anti-inflammatory drugs (NSAIDs). We tested the hypotheses that (i) adverse CV events reported among ADAPT participants (aged 70 years and older) are associated with increased ratio of urine 11-dehydrothromboxane B2 (Tx-M) to 2′3-donor–6-keto-PGF1 (PGI-M) attributable to NSAID treatments; (ii) coincident use of aspirin (ASA) would attenuate NSAID-induced changes in Tx-M/PGI-M ratio; and (iii) use of NSAIDs and/or ASA would not alter urine or plasma concentrations of F2-isoprostanes (IsoPs), in vivo biomarkers of free radical damage. We quantified urine Tx-M and PGI-M, and urine and plasma F2-IsoPs from 315 ADAPT participants using stable isotope dilution assays with gas chromatography/mass spectrometry, and analyzed these data by randomized drug assignment and self-report compliance as well as ASA use. Adverse CV events were significantly associated with higher urine Tx-M/PGI-M ratio, which seemed to derive mainly from lowered PGI-M. Participants taking ASA alone had reduced urine Tx-M/PGI-M compared to no ASA or NSAID; however, participants taking NSAIDs plus ASA did not have reduced urine Tx-M/PGI-M ratio compared to NSAIDs alone. Neither NSAID nor ASA use altered plasma or urine F2-IsoPs. These data suggest a possible mechanism for the increased risk of CV events reported in ADAPT participants assigned to NSAIDs, and suggest that the changes in the Tx-M/PGI-M ratio was not substantively mitigated by coincident use of ASA in individuals 70 years or older

Lipoxygenases and Poly(ADP-Ribose) Polymerase in Amyloid Beta Cytotoxicity

The 12/15-lipoxygenase(s) (LOX), poly(ADP-ribose) polymerase (PARP-1) activity and mitochondrial apoptosis inducing factor (AIF) protein in the amyloid β (Aβ) toxicity were investigated in PC12 cells that express either wild-type (APPwt) or double Swedish mutation (APPsw) forms of human Aβ precursor protein. Different levels of Aβ secretion and free radicals formation characterize these cells. The results demonstrated a relationship between the Aβ levels and LOX protein expression and activity. High Aβ concentration in APPsw cells correlated with a significant increase in free radicals and LOX activation, which leads to translocation of p65/NF-κB into the nucleus. An increase in AIF expression in mitochondria was observed concurrently with inhibition of PARP-1 activity in the nuclear fraction of APPsw cells. We suggested that AIF accumulation in mitochondria may be involved in adaptive/protective processes. However, inhibition of PARP-1 may be responsible for the disturbances in transcription and DNA repair as well as the degeneration of APP cells. Under conditions of increased nitrosative stress, evoked by the nitric oxide donor, sodium nitroprusside (SNP, 0.5 mM), 70–80% of all cells types died after 24 h, significantly more in APPsw cells. There was no further significant change in mitochondrial AIF level and PARP-1 activity compared to corresponding non-treated cells. Only one exception was observed in PC12 control, where SNP significantly inhibits PARP-1 activity. Moreover, SNP significantly activated gene expression for 12/15-LOX in all types of investigated cells. Inhibitors of all LOX isoforms and specific inhibitor of 12-LOX enhanced the survival of cells that were subjected to SNP. We conclude that the LOX pathways may play a role in Aβ toxicity and in nitrosative-stress-induced cell death and that inhibition of these pathways offers novel protective strategies